Research Perspective Volume 3, Issue 12 pp 1154—1162

Recent progress in targeting cancer

Zoya N. Demidenko1, , James A. McCubrey2, ,

  • 1 Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA
  • 2 Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

Received: December 5, 2011       Accepted: December 28, 2011       Published: December 31, 2011
How to Cite

Copyright: © 2011 Demidenko et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer.

In 1977, Andrzej “Andrew” V. Schally won Nobel Prize in medicine for his research into peptide hormone production in the brain. He described the neurohormone GnRH and other releasing hormones (RH). As initially unexpected application, agonists and antagonists of these hormones have become investigational anti-cancer agents [1-3]. As further developments, Schally and coworkers described targeting gastrin releasing peptide receptors. Gastrin-releasing peptide (GRP) is involved in cancer growth and GRP receptors are expressed in a variety of cancer cells and have limited distribution in normal human tissue. Thus inhibition of GRP receptors represents an attractive target for pharmacological treatment of certain human malignancies [4]. Also, MZ-5-156, an antagonist of growth hormone-releasing hormone (GHRH), decreased cell proliferation and activated AMPK and inhibited Akt, the mammalian target of rapamycin (mTOR) and its downstream target eIF4E which controls protein synthesis and cell growth [5]. GHRH antagonists also caused cell cycle arrest and apoptosis in human colon cancer cells [6, 7].

Yet, this is only one of hundreds examples for new therapeutic targets and new types of drugs that have been developed recently in cellular and animal models. Searche for new targets has continued with many promising lead compounds identified [8-38].

Among promising targets are cancer stem cells [39-42], microRNAs [43-50], the MEK/ERK pathway [51-64] and especially its upstream activator BRAF [61, 65-67] and the NF-kB pathway [68], Myc and HIF-1 [69-72], The CtBP transcriptional corepressors [73], Polycomb group (PcG) proteins [74], autophagy [75-77], translation [78], the proteasome [35], HSP70 [79, 80], Hsp90 [81-84], the AMPK-FoxO3A axis [85], STAT3 and MEK/ERK/BCL-2 signaling [86], the Hh signal transducer Smoothened [87], ErbBs receptor tyrosine kinases [88], and anti-apoptotic members of the Bcl-2 family, Bcl-2, Bcl-X(L) and Mcl-1 [89]. Stromal and endothelial cells are also targets [90, 91]. There are also new targets for anti-angiogenic therapy [71, 75, 78, 92-94]. Also, epithelial mesenchymal transition (EMT) is a critical mechanism for the acquisition of malignant phenotypes by epithelial cells [95]. In colorectal cancer, such cells are histologically represented by tumor buds defined as single cells or small clusters of de-differentiated tumor cells at the invasive front. These buds are also considered as targets for novel cancer therapy [96, 97]. Recently, leukocytes in the ovarian cancer microenvironment such as regulatory T cells and immature pro-angiogenic myeloid cells have been demonstrated to play a fundamental role in tumor progression and have been suggested as potential target [98]. Cdk4/6 is an attractive target for cancer therapy. Thus, a 2-aminothiazole-derived Cdk4/6 selective inhibitor, named Compound A potently inhibits Cdk4 and Cdk6 with high selectivity [99]. Among 82 human cell line examined, leukemia and lymphoma cell lines tended to be more sensitive to Compound A. In a nude rat xenograft model, Compound A inhibited cell proliferation in xenograft tumors at a plasma concentration of 510 nM. Compound A only moderately inhibited cell cycle progression of normal crypt cells in small intestine even at 5 times higher plasma concentration and did not cause immunosuppression even at 17 times higher concentration [99].

Targeting the androgen receptor also has also shown significant progress [100-103]. An interesting example is targeting androgen receptor in estrogen receptor-negative breast cancer [104]. Also, a small-molecule inhibitor of the amino-terminus domain of the androgen receptor causes regression of castrate-recurrent prostate cancer [105, 106]. Recent discoveries revealed a transcription-independent function of androgen receptor that is essential for prostate cancer cell viability and, therefore, is an ideal target for anticancer treatment. Several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization [107].

Among numerous new experimental therapeutics, a small-molecule inducer of polyploidy, R1530, interferes with tubulin polymerization, leads to abortive mitosis, endoreduplication and polyploidy. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. BubR1 plays a key role in polyploidy induction by R1530 and could be exploited as a target for designing more specific polyploidy inducers [108]. Vosaroxin (formerly voreloxin) is a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, inducing site-selective double-strand breaks (DSB), G2 arrest and apoptosis. Homologous recombination repair (HRR) is critical for recovery from DNA damage induced by both agents, identifying the potential to clinically exploit synthetic lethality [109]. Depletion of POLQ (DNA polymerase theta) renders tumor cells more sensitive to radiotherapy without effecting normal tissues, providing ways to increase therapeutic window [110]. Mycoplasma is also a target for cancer prevention [111] and therapy [112]. Among additional targets is activating transcription factor 5 (ATF5), an anti-apoptotic protein that is highly expressed in malignant glioma but not normal brain tissues, and is essential for glioma cell survival [113].

There were several developments in targeting p53 and its cousins, p73 and p63 [114-121]. Nutlin-3a is a non-genotoxic inducer of p53 and causes the transcription-independent mitochondrial p53 program of nutlin-induced apoptosis in tumor cells [122] p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA [123]. A new therapeutic basis for treating Li-Fraumeni syndrome breast tumors expressing mutated p53 has been suggested [124]. Importang breakthrough was the development of curaxins: anticancer compounds that simultaneously suppress NF-kB and activate p53 by targeting FACT [30, 125, 126].

There was continued development of new ways of drug delivery including liposomes and nanoparticles [91, 127-130]. There are several highly innovative strategies such as targeting tumors with Salmonella Typhimurium [131-133] and use of low-level doses of [(32)P]ATP to inhibit tumor growth [134]. Several cancer treatment approaches, such as proteasome inhibitor Bortezomib and hsp90 inhibitor geldanamycin, involve accumulation of misfolded proteins creating proteotoxic stress. Low efficacy of these therapies is likely due to the protective effects of heat shock response (HSR) induced in treated cells, making this pathway an attractive target for pharmacological suppression. It was shown that the anti-malaria drugs quinacrine prevented HSR in cancer cells. Quinacrine did not affect protein synthesis, but rather suppressed inducible HSF1-dependent transcription of the hsp70 gene. A combination of non-toxic concentrations of quinacrine and proteotoxic stress inducers resulted in rapid induction of apoptosis in cancer cells. Therefore, quinacrine, a non-toxic drug long used for treatment of malaria, has significant clinical potential in cancer therapy [80, 135-137]. Another example is proteotoxic stress targeted therapy (PSTT), where the induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor Bortezomib [138]. Also it was shown that hypoxia enhances the replication of oncolytic herpes simplex virus in p53- breast cancer cells [139].

Aerobic glycolysis, characterized by high glucose uptake, low oxygen consumption and elevated production of lactate, is associated with a survival advantage and is a hallmark of cancer. Targeting key metabolic enzymes involved in glycolysis may provide a novel therapeutic approach [140-145].

There was also further development of the concept of synthetic lethality [146-149]. Synthetic lethal interactions between mutated oncogenes/tumor suppressor genes and molecules involved in DNA damage signaling and repair can be therapeutically exploited to preferentially kill tumor cells [150]. As another example of synthetic lethality, activation of mTOR by targeting TSC2 is toxic in cancer cells lacking Rb [151, 152].

Intriguingly, activation of mTOR converts arrest caused by p53 into senescence [153-156]. And vice versa, inhibition of mTOR allows arrested cells to avoid senescence, remaining merely quiescent. This is in agreement with the notion that mTOR is involved in aging and aging and age-related diseases [157, 158].

There was also further development of the concept of protection of normal cells [159]. Pre-treatment with low doses of actinomycin D, a clinically-approved drug and potent p53 activator, before adding the aurora kinase inhibitor VX-680 protected normal fibroblasts from polyploidy and nuclear morphology abnormalities induced by VX-680 [160]. Similarly, normal cells could be protected from cytotoxic chemotherapy by nutlin-3a, actinomycin, rapamycin and metformin alone or in combinations [161-163]. Several other strategies to protect normal cells are under development [164-166].

As a side effect, CPT-11 can cause severe diarrhea caused by symbiotic bacterial beta-glucuronidases that reactivate the drug in the gut. The strategy was suggested to target these enzymes without killing the bacteria essential for human health. Bacterial beta-glucuronidase inhibitors were identified, which have no effect on the orthologous mammalian enzyme. Inhibitors were effective against the enzyme target in living bacteria, but did not kill the bacteria or harm mammalian cells. Oral administration of an inhibitor protected mice from CPT-11-induced toxicity [167]. In another study, transgenic mice overexpressing p53 were protected from the gastrointestinal syndrome after irradiation. This suggests that the gastrointestinal syndrome is caused by the death of gastrointestinal epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis [168]. While inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, therapeutic antibody targeting of individual Notch receptors avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors [169]. Interestingly, chromosomal instability (CIN) is associated with intrinsic resistance to taxanes, acquired multidrug resistance and poor prognosis. In contrast, platinum agents may specifically target CIN cancers [170].

In addition to quinacrine, other well known, non-toxic drugs are under re-development for cancer therapy. One of them is metformin, an anti-diabetic drug [171-186]. Several research groups observed that breast cancer patients receiving beta-blockers for hypertension had reduced metastasis and improved clinical outcome. Medical records revealed that beta-blocker treated patients showed a significant reduction in metastasis development, tumor recurrence, and longer disease free interval after surgery. In addition, there was a reduced risk of metastasis and a reduction in breast cancer mortality [187-189]. This finding was further confirmed [190-192]. Another advance is to use of Angiotensin II type 1 receptor blockers in ER-positive and ERBB2-negative breast cancer cases [193].

Thus there have been significant advances to the targeting of various cancers, both with selective inhibitors and with drugs such as rapamycin and metformin which have been used to treat organ transplant patients and diabetics respectively. Further studies will continue to evaluate the effectiveness of targeting the various pathways mentioned in this review with signal transduction inhibitors, natural products, chemotherapeutic drugs and drugs used for different medial purposes either by themselves or in various intelligent combinations based on the knowledge of the critical signal transduction pathways altered in the particular cancer cell.

Conflicts of Interest

The authors of this manuscript have no conflict of interest to declare.


  • 1. Redding TW and Schally AV. Inhibition of cell growth by a hypothalamic peptide. Proc Natl Acad Sci U S A. 1982; 79:7014-7018. [PubMed]
  • 2. Barabutis N and Schally AV. Growth hormone-releasing hormone: extrapituitary effects in physiology and pathology. Cell Cycle. 2010; 9:4110-4116. [PubMed]
  • 3. Schally AV, Varga JL, Engel JB. Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab. 2008; 4:33-43. [PubMed]
  • 4. Hohla F and Schally AV. Targeting gastrin releasing peptide receptors: New options for the therapy and diagnosis of cancer. Cell Cycle. 2010; 9:1738-1741. [PubMed]
  • 5. Siejka A, Barabutis N, Schally AV. GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells. Cell Cycle. 2011; 10:3714-3718. [PubMed]
  • 6. Hohla F, Buchholz S, Schally AV, Seitz S, Rick FG, Szalontay L, Varga JL, Zarandi M, Halmos G, Vidaurre I, Krishan A, Kurtoglu M, Chandna S, Aigner E, Datz C. GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells. Cell Cycle. 2009; 8:3149-3156. [PubMed]
  • 7. Kiaris H, Chatzistamou I, Papavassiliou AG, Schally AV. Growth hormone-releasing hormone: not only a neurohormone. Trends Endocrinol Metab. 2011; 22:311-317. [PubMed]
  • 8. Tyner J and Druker BJ. RNAi screen for therapeutic target in leukemia. Cell Cycle. 2009; 8:2144 [PubMed]
  • 9. Qiao M, Shi Q, Pardee AB. The pursuit of oncotargets through understanding defective cell regulation. Oncotarget. 2010; 1:544-551. [PubMed]
  • 10. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio AL, Dias SM, Dang CV, Cerione RA. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell. 2011; 18:207-219. [PubMed]
  • 11. Schnaiter A and Stilgenbauer S. Refractory chronic lymphocytic leukemia–new therapeutic strategies. Oncotarget. 2010; 1:472-482. [PubMed]
  • 12. D'Agostino L and Giordano A. NSP 5a3a: a potential novel cancer target in head and neck carcinoma. Oncotarget. 2010; 1:423-435. [PubMed]
  • 13. Murai R, Yoshida Y, Muraguchi T, Nishimoto E, Morioka Y, Kitayama H, Kondoh S, Kawazoe Y, Hiraoka M, Uesugi M, Noda M. A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs. Oncotarget. 2010; 1:252-264. [PubMed]
  • 14. Chen L, Yang S, Jakoncic J, Zhang JJ, Huang XY. Migrastatin analogues target fascin to block tumour metastasis. Nature. 464:1062-1066. [PubMed]
  • 15. Telerman A, Amson R, Hendrix MJ. Tumor reversion holds promise. Oncotarget. 2010; 1:233-234. [PubMed]
  • 16. Anders L, Ke N, Hydbring P, Choi YJ, Widlund HR, Chick JM, Zhai H, Vidal M, Gygi SP, Braun P, Sicinski P. A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. Cancer Cell. 2011; 20:620-634. [PubMed]
  • 17. Kelber JA and Klemke RL. PEAK1, a novel kinase target in the fight against cancer. Oncotarget. 2010; 1:219-223. [PubMed]
  • 18. Peng C, Chen Y, Li D, Li S. Role of Pten in leukemia stem cells. Oncotarget. 2010; 1:156-160. [PubMed]
  • 19. Zhang B, Strauss AC, Chu S, Li M, Ho Y, Shiang KD, Snyder DS, Huettner CS, Shultz L, Holyoake T, Bhatia R. Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate. Cancer Cell. 2010; 17:427-442. [PubMed]
  • 20. Van Etten RA. BCL6: a novel target for therapy of Ph+ B cell acute lymphoblastic leukemia. Cancer Cell. 2011; 20:3-5. [PubMed]
  • 21. Cerchietti LC, Ghetu AF, Zhu X, Da Silva GF, Zhong S, Matthews M, Bunting KL, Polo JM, Fares C, Arrowsmith CH, Yang SN, Garcia M, Coop A, Mackerell AD Jr., Prive GG, Melnick A. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell. 2010; 17:400-411. [PubMed]
  • 22. Hobbs RM and Pandolfi PP. Shape-shifting and tumor suppression by PLZF. Oncotarget. 2010; 1:3-5. [PubMed]
  • 23. Erickson JW and Cerione RA. Glutaminase: a hot spot for regulation of cancer cell metabolism? Oncotarget. 2010; 1:734-740. [PubMed]
  • 24. Staquicini FI, Ozawa MG, Moya CA, Driessen WH, Barbu EM, Nishimori H, Soghomonyan S, Flores LG 2nd, Liang X, Paolillo V, Alauddin MM, Basilion JP, Furnari FB, Bogler O, Lang FF, Aldape KD, et al. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma. J Clin Invest. 2011; 121:161-173. [PubMed]
  • 25. Duncan CG, Killela PJ, Payne CA, Lampson B, Chen WC, Liu J, Solomon D, Waldman T, Towers AJ, Gregory SG, McDonald KL, McLendon RE, Bigner DD, Yan H. Integrated genomic analyses identify ERRFI1 and TACC3 as glioblastoma-targeted genes. Oncotarget. 2010; 1:265-277. [PubMed]
  • 26. Frezza C, Zheng L, Folger O, Rajagopalan KN, MacKenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, et al. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature. 2011; 477:225-228. [PubMed]
  • 27. Ionov Y. A high throughput method for identifying personalized tumor-associated antigens. Oncotarget. 2010; 1:148-155. [PubMed]
  • 28. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, et al. The genetic landscape of the childhood cancer medulloblastoma. Science. 2011; 331:435-439. [PubMed]
  • 29. Heminger K, Markey M, Mpagi M, Berberich SJ. Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53. Aging (Albany NY). 2009; 1:89-108. [PubMed]
  • 30. Gasparian AV, Burkhart CA, Purmal AA, Brodsky L, Pal M, Saranadasa M, Bosykh DA, Commane M, Guryanova OA, Pal S, Safina A, Sviridov S, Koman IE, Veith J, Komar AA, Gudkov AV, et al. Curaxins: anticancer compounds that simultaneously suppress NF-kappaB and activate p53 by targeting FACT. Sci Transl Med. 2011; 3:95ra74.
  • 31. Chang CY, Kazmin D, Jasper JS, Kunder R, Zuercher WJ, McDonnell DP. The metabolic regulator ERRalpha, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer. Cancer Cell. 2011; 20:500-510. [PubMed]
  • 32. Blobel GA, Kalota A, Sanchez PV, Carroll M. Short hairpin RNA screen reveals bromodomain proteins as novel targets in acute myeloid leukemia. Cancer Cell. 2011; 20:287-288. [PubMed]
  • 33. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, Taylor MJ, Johns C, Chicas A, Mulloy JC, Kogan SC, Brown P, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011; 478:524-528. [PubMed]
  • 34. Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med. 2011; 17:1685-1691. [PubMed]
  • 35. D'Arcy P, Brnjic S, Olofsson MH, Fryknas M, Lindsten K, De Cesare M, Perego P, Sadeghi B, Hassan M, Larsson R, Linder S. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011; 17:1636-1640. [PubMed]
  • 36. Giamas G, Filipovic A, Jacob J, Messier W, Zhang H, Yang D, Zhang W, Shifa BA, Photiou A, Tralau-Stewart C, Castellano L, Green AR, Coombes RC, Ellis IO, Ali S, Lenz HJ, et al. Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer. Nat Med. 2011; 17:715-719. [PubMed]
  • 37. Ni X, Zhang Y, Ribas J, Chowdhury WH, Castanares M, Zhang Z, Laiho M, DeWeese TL, Lupold SE. Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts. J Clin Invest. 2011; 121:2383-2390. [PubMed]
  • 38. Zhu Z, Zhong S, Shen Z. Targeting the inflammatory pathways to enhance chemotherapy of cancer. Cancer Biol Ther. 2011; 12:95-105. [PubMed]
  • 39. Kemper K, Grandela C, Medema JP. Molecular identification and targeting of colorectal cancer stem cells. Oncotarget. 2010; 1:387-395. [PubMed]
  • 40. Curtin JC and Lorenzi MV. Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget. 2010; 1:563-577. [PubMed]
  • 41. Chen Y, Li D, Li S. The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. Cell Cycle. 2009; 8:3488-3492. [PubMed]
  • 42. McCubrey JA, Abrams SL, Umezawa K, Cocco L, Martelli AM, Franklin RA, Chappell WH, Steelman LS. Novel approaches to target cancer initiating cells-Eliminating the root of the cancer. Adv Enzyme Regul. 2011;.
  • 43. Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Wurdinger T. miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget. 2010; 1:710-720. [PubMed]
  • 44. Konopleva MY and Jordan CT. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J Clin Oncol. 2011; 29:591-599. [PubMed]
  • 45. Noonan EJ, Place RF, Basak S, Pookot D, Li LC. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells. Oncotarget. 2010; 1:349-358. [PubMed]
  • 46. Mavrakis KJ and Wendel HG. TargetScreen: an unbiased approach to identify functionally important microRNA targets. Cell Cycle. 2010; 9:2080-2084. [PubMed]
  • 47. Kotani A, Ha D, Schotte D, den Boer ML, Armstrong SA, Lodish HF. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells. Cell Cycle. 2010; 9:1037-1042. [PubMed]
  • 48. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9:775-789. [PubMed]
  • 49. Pekarsky Y and Croce CM. Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget. 2010; 1:224-227. [PubMed]
  • 50. Pan X, Wang ZX, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2011; 10:1224-1232. [PubMed]
  • 51. Sacco A, Roccaro A, Ghobrial IM. Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia. Oncotarget. 2010; 1:578-582. [PubMed]
  • 52. Martelli AM, Evangelisti C, Chiarini F, McCubrey JA. The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget. 2010; 1:89-103. [PubMed]
  • 53. Evangelisti C, Ricci F, Tazzari P, Tabellini G, Battistelli M, Falcieri E, Chiarini F, Bortul R, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Martelli AM. Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia. Leukemia. 2011; 25:781-791. [PubMed]
  • 54. Benjamin D, Colombi M, Moroni C, Hall MN. Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov. 2011; 10:868-880. [PubMed]
  • 55. Guillard S, Clarke PA, Te Poele R, Mohri Z, Bjerke L, Valenti M, Raynaud F, Eccles SA, Workman P. Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma. Cell Cycle. 2009; 8:443-453. [PubMed]
  • 56. Janes MR and Fruman DA. Targeting TOR dependence in cancer. Oncotarget. 2010; 1:69-76. [PubMed]
  • 57. Dbouk HA and Backer JM. A beta version of life: p110beta takes center stage. Oncotarget. 2010; 1:729-733. [PubMed]
  • 58. Markman B, Dienstmann R, Tabernero J. Targeting the PI3K/Akt/mTOR pathway–beyond rapalogs. Oncotarget. 2010; 1:530-543. [PubMed]
  • 59. Zawel L. P3Kalpha: a driver of tumor metastasis? Oncotarget. 2010; 1:315-316. [PubMed]
  • 60. Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY). 2009; 1:515-528. [PubMed]
  • 61. Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D'Andrea K, Pushparajan A, Hayden JE, Brown KD, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010; 18:683-695. [PubMed]
  • 62. Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA, Vu C, Lilly MB, Mallya S, Ong ST, Konopleva M, Martin MB, Ren P, Liu Y, Rommel C, Fruman DA. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med. 2010; 16:205-213. [PubMed]
  • 63. Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest. 2011; 121:1231-1241. [PubMed]
  • 64. Chen C, Liu Y, Zheng P. Mammalian target of rapamycin activation underlies HSC defects in autoimmune disease and inflammation in mice. J Clin Invest. 2010; 120:4091-4101. [PubMed]
  • 65. Nucera C, Lawler J, Hodin R, Parangi S. The BRAFV600E mutation: what is it really orchestrating in thyroid cancer? Oncotarget. 2010; 1:751-756. [PubMed]
  • 66. Vultur A, Villanueva J, Herlyn M. BRAF inhibitor unveils its potential against advanced melanoma. Cancer Cell. 2010; 18:301-302. [PubMed]
  • 67. Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, Burton EA, Wong B, Tsang G, West BL, Powell B, Shellooe R, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010; 467:596-599. [PubMed]
  • 68. Demchenko YN and Kuehl WM. A critical role for the NFkB pathway in multiple myeloma. Oncotarget. 2010; 1:59-68. [PubMed]
  • 69. Podar K and Anderson KC. A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways. Cell Cycle. 2010; 9:1722-1728. [PubMed]
  • 70. Qi J, Pellecchia M, Ronai ZA. The Siah2-HIF-FoxA2 axis in prostate cancer - new markers and therapeutic opportunities. Oncotarget. 2010; 1:379-385. [PubMed]
  • 71. Rapisarda A, Shoemaker RH, Melillo G. Antiangiogenic agents and HIF-1 inhibitors meet at the crossroads. Cell Cycle. 2009; 8:4040-4043. [PubMed]
  • 72. Kuo MT, Savaraj N, Feun LG. Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes. Oncotarget. 2010; 1:246-251. [PubMed]
  • 73. Straza MW, Paliwal S, Kovi RC, Rajeshkumar B, Trenh P, Parker D, Whalen GF, Lyle S, Schiffer CA, Grossman SR. Therapeutic targeting of C-terminal binding protein in human cancer. Cell Cycle. 2010; 9:3740-3750. [PubMed]
  • 74. Bommi PV, Dimri M, Sahasrabuddhe AA, Khandekar J, Dimri GP. The polycomb group protein BMI1 is a transcriptional target of HDAC inhibitors. Cell Cycle. 2010; 9:2663-2673. [PubMed]
  • 75. Li X, Kumar A, Zhang F, Lee C, Li Y, Tang Z, Arjuna P. VEGF-independent angiogenic pathways induced by PDGF-C. Oncotarget. 2010; 1:309-314. [PubMed]
  • 76. Puissant A, Robert G, Auberger P. Targeting autophagy to fight hematopoietic malignancies. Cell Cycle. 2010; 9:3470-3478. [PubMed]
  • 77. Huang Y and Ratovitski EA. Phospho-DeltaNp63alpha/Rpn13-dependent regulation of LKB1 degradation modulates autophagy in cancer cells. Aging (Albany NY). 2010; 2:959-968. [PubMed]
  • 78. Taraboletti G, Rusnati M, Ragona L, Colombo G. Targeting tumor angiogenesis with TSP-1-based compounds: rational design of antiangiogenic mimetics of endogenous inhibitors. Oncotarget. 2010; 1:662-673. [PubMed]
  • 79. Powers MV, Jones K, Barillari C, Westwood I, van Montfort RL, Workman P. Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle. 2010; 9:1542-1550. [PubMed]
  • 80. Neznanov N, Gorbachev AV, Neznanova L, Komarov AP, Gurova KV, Gasparian AV, Banerjee AK, Almasan A, Fairchild RL, Gudkov AV. Anti-malaria drug blocks proteotoxic stress response: anti-cancer implications. Cell Cycle. 2009; 8:3960-3970. [PubMed]
  • 81. Cerchietti LC, Lopes EC, Yang SN, Hatzi K, Bunting KL, Tsikitas LA, Mallik A, Robles AI, Walling J, Varticovski L, Shaknovich R, Bhalla KN, Chiosis G, Melnick A. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat Med. 2009; 15:1369-1376. [PubMed]
  • 82. Beloueche-Babari M, Arunan V, Jackson LE, Perusinghe N, Sharp SY, Workman P, Leach MO. Modulation of melanoma cell phospholipid metabolism in response to heat shock protein 90 inhibition. Oncotarget. 2010; 1:185-197. [PubMed]
  • 83. De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, et al. Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proc Natl Acad Sci U S A. 2010; 108:11878-11883. [PubMed]
  • 84. Kang BH, Tavecchio M, Goel HL, Hsieh CC, Garlick DS, Raskett CM, Lian JB, Stein GS, Languino LR, Altieri DC. Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease. Br J Cancer. 2011; 104:629-634. [PubMed]
  • 85. Chiacchiera F and Simone C. The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle. 2010; 9:1091-1096. [PubMed]
  • 86. Shi L, Wang S, Zangari M, Xu H, Cao TM, Xu C, Wu Y, Xiao F, Liu Y, Yang Y, Salama M, Li G, Tricot G, Zhan F. Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance. Oncotarget. 2010; 1:22-33. [PubMed]
  • 87. Jagani Z, Dorsch M, Warmuth M. Hedgehog pathway activation in chronic myeloid leukemia. Cell Cycle. 2010; 9:3449-3456. [PubMed]
  • 88. Rudloff U and Samuels Y. A growing family: adding mutated Erbb4 as a novel cancer target. Cell Cycle. 2010; 9:1487-1503. [PubMed]
  • 89. Straten P and Andersen MH. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens. Oncotarget. 2010; 1:239-245. [PubMed]
  • 90. Liu D, Martin V, Fueyo J, Lee OH, Xu J, Cortes-Santiago N, Alonso MM, Aldape K, Colman H, Gomez-Manzano C. Tie2/TEK modulates the interaction of glioma and brain tumor stem cells with endothelial cells and promotes an invasive phenotype. Oncotarget. 2010; 1:700-709. [PubMed]
  • 91. Mann AP, Bhavane RC, Somasunderam A, Liz Montalvo-Ortiz B, Ghaghada KB, Volk D, Nieves-Alicea R, Suh KS, Ferrari M, Annapragada A, Gorenstein DG, Tanaka T. Thioaptamer conjugated liposomes for tumor vasculature targeting. Oncotarget. 2011; 2:298-304. [PubMed]
  • 92. Weis SM and Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011; 17:1359-1370. [PubMed]
  • 93. Mulder K, Koski S, Scarfe A, Chu Q, King K, Spratlin J. Antiangiogenic agents in advanced gastrointestinal malignancies: past, present and a novel future. Oncotarget. 2010; 1:515-529. [PubMed]
  • 94. Tvorogov D, Anisimov A, Zheng W, Leppanen VM, Tammela T, Laurinavicius S, Holnthoner W, Helotera H, Holopainen T, Jeltsch M, Kalkkinen N, Lankinen H, Ojala PM, Alitalo K. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell. 2010; 18:630-640. [PubMed]
  • 95. Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, Settleman J. A gene expression signature associated with “K-Ras addiction” reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009; 15:489-500. [PubMed]
  • 96. Zlobec I and Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget. 2010; 1:651-661. [PubMed]
  • 97. Yamaguchi H and Oikawa T. Membrane lipids in invadopodia and podosomes: key structures for cancer invasion and metastasis. Oncotarget. 2010; 1:320-328. [PubMed]
  • 98. Cubillos-Ruiz JR, Rutkowski M, Conejo-Garcia JR. Blocking ovarian cancer progression by targeting tumor microenvironmental leukocytes. Cell Cycle. 2010; 9:260-268. [PubMed]
  • 99. Hirai H, Shimomura T, Kobayashi M, Eguchi T, Taniguchi E, Fukasawa K, Machida T, Oki H, Arai T, Ichikawa K, Hasako S, Haze K, Kodera T, Kawanishi N, Takahashi-Suziki I, Nakatsuru Y, et al. Biological characterization of 2-aminothiazole-derived Cdk4/6 selective inhibitor in vitro and in vivo. Cell Cycle. 2010; 9:1590-1600. [PubMed]
  • 100. Tararova ND, Narizhneva N, Krivokrisenko V, Gudkov AV, Gurova KV. Prostate cancer cells tolerate a narrow range of androgen receptor expression and activity. Prostate. 2007; 67:1801-1815. [PubMed]
  • 101. Thompson TC. Grappling with the androgen receptor: a new approach for treating advanced prostate cancer. Cancer Cell. 2010; 17:525-526. [PubMed]
  • 102. Rokhlin OW, Guseva NV, Taghiyev AF, Glover RA, Cohen MB. KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer. Cancer Biol Ther. 2010; 9:224-235. [PubMed]
  • 103. Jonsson JG, Sissung TM, Figg WD. A genomic strategy for predicting androgen receptor activity in prostate tumors. Cancer Biol Ther. 2009; 8:2002-2003. [PubMed]
  • 104. Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell. 2011; 20:119-131. [PubMed]
  • 105. Andersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung JK, Watt K, Tam T, Yang YC, Banuelos CA, Williams DE, McEwan IJ, Wang Y, Sadar MD. Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell. 2010; 17:535-546. [PubMed]
  • 106. Gioeli DG. The promise of novel androgen receptor antagonists. Cell Cycle. 2010; 9:440-441. [PubMed]
  • 107. Narizhneva NV, Tararova ND, Ryabokon P, Shyshynova I, Prokvolit A, Komarov PG, Purmal AA, Gudkov AV, Gurova KV. Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer. Cell Cycle. 2009; 8:4155-4167. [PubMed]
  • 108. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle. 2010; 9:3364-3375. [PubMed]
  • 109. Hawtin RE, Stockett DE, Wong OK, Lundin C, Helleday T, Fox JA. Homologous recombination repair is essential for repair of vosaroxin-induced DNA double-strand breaks. Oncotarget. 2010; 1:606-619. [PubMed]
  • 110. Higgins GS, Harris AL, Prevo R, Helleday T, McKenna WG, Buffa FM. Overexpression of POLQ confers a poor prognosis in early breast cancer patients. Oncotarget. 2010; 1:175-184. [PubMed]
  • 111. Barykova YA, Logunov DY, Shmarov MM, Vinarov AZ, Fiev DN, Vinarova NA, Rakovskaya IV, Baker PS, Shyshynova I, Stephenson AJ, Klein EA, Naroditsky BS, Gintsburg AL, Gudkov AV. Association of Mycoplasma hominis infection with prostate cancer. Oncotarget. 2011; 2:289-297. [PubMed]
  • 112. Liekens S, Bronckaers A, Balzarini J. Improvement of purine and pyrimidine antimetabolite-based anticancer treatment by selective suppression of mycoplasma-encoded catabolic enzymes. Lancet Oncol. 2009; 10:628-635. [PubMed]
  • 113. Sheng Z, Evans SK, Green MR. An activating transcription factor 5-mediated survival pathway as a target for cancer therapy? Oncotarget. 2010; 1:457-460. [PubMed]
  • 114. Selivanova G. Therapeutic targeting of p53 by small molecules. Semin Cancer Biol. 2010; 20:46-56. [PubMed]
  • 115. Zawacka-Pankau J, Kostecka A, Sznarkowska A, Hedstrom E, Kawiak A. p73 tumor suppressor protein: a close relative of p53 not only in structure but also in anti-cancer approach? Cell Cycle. 2010; 9:720-728. [PubMed]
  • 116. Zawacka-Pankau J, Grinkevich VV, Hunten S, Nikulenkov F, Gluch A, Li H, Enge M, Kel A, Selivanova G. Inhibition of Glycolytic Enzymes Mediated by Pharmacologically Activated p53: TARGETING WARBURG EFFECT TO FIGHT CANCER. J Biol Chem. 2011; 286:41600-41615. [PubMed]
  • 117. Grinkevich VV, Nikulenkov F, Shi Y, Enge M, Bao W, Maljukova A, Gluch A, Kel A, Sangfelt O, Selivanova G. Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Cancer Cell. 2009; 15:441-453. [PubMed]
  • 118. de Lange J, Ly LV, Lodder K, Verlaan-de Vries M, Teunisse AF, Jager MJ, Jochemsen AG. Synergistic growth inhibition based on small-molecule p53 activation as treatment for intraocular melanoma. Oncogene. 2011;.
  • 119. Chung J and Irwin MS. Targeting the p53-family in cancer and chemosensitivity: triple threat. Curr Drug Targets. 2010; 11:667-681. [PubMed]
  • 120. Bykov VJ, Lambert JM, Hainaut P, Wiman KG. Mutant p53 rescue and modulation of p53 redox state. Cell Cycle. 2009; 8:2509-2517. [PubMed]
  • 121. Li D, Marchenko ND, Moll UM. SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ. 2011; 18:1904-1913. [PubMed]
  • 122. Vaseva AV, Marchenko ND, Moll UM. The transcription-independent mitochondrial p53 program is a major contributor to nutlin-induced apoptosis in tumor cells. Cell Cycle. 2009; 8:1711-1719. [PubMed]
  • 123. Hedstrom E, Eriksson S, Zawacka-Pankau J, Arner ES, Selivanova G. p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA. Cell Cycle. 2009; 8:3576-3583. [PubMed]
  • 124. Glazer RI. A new therapeutic basis for treating Li-Fraumeni Syndrome breast tumors expressing mutated TP53. Oncotarget. 2010; 1:470-471. [PubMed]
  • 125. Garcia H, Fleyshman D, Kolesnikova K, Safina A, Commane M, Paszkiewicz G, Omelian A, Morrison C, Gurova K. Expression of FACT in mammalian tissues suggests its role in maintaining of undifferentiated state of cells. Oncotarget. 2011; 2:783-796. [PubMed]
  • 126. Draetta GF and Depinho RA. Cancer drug discovery faces the FACT. Sci Transl Med. 2011; 3:95ps34.
  • 127. Basu S, Chaudhuri P, Sengupta S. Targeting oncogenic signaling pathways by exploiting nanotechnology. Cell Cycle. 2009; 8:3480-3487. [PubMed]
  • 128. Qiao Y, Huang X, Nimmagadda S, Bai R, Staedtke V, Foss CA, Cheong I, Holdhoff M, Kato Y, Pomper MG, Riggins GJ, Kinzler KW, Diaz LA Jr., Vogelstein B, Zhou S. A robust approach to enhance tumor-selective accumulation of nanoparticles. Oncotarget. 2010; 2:59-68. [PubMed]
  • 129. Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM, Hanahan D, Mattrey RF, Ruoslahti E. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell. 2009; 16:510-520. [PubMed]
  • 130. Lim KJ, Bisht S, Bar EE, Maitra A, Eberhart CG. A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. Cancer Biol Ther. 11:464-473. [PubMed]
  • 131. Wall DM, Srikanth CV, McCormick BA. Targeting tumors with salmonella Typhimurium- potential for therapy. Oncotarget. 2010; 1:721-728. [PubMed]
  • 132. Nguyen VH, Kim HS, Ha JM, Hong Y, Choy HE, Min JJ. Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res. 2010; 70:18-23. [PubMed]
  • 133. Liu F, Zhang L, Hoffman RM, Zhao M. Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity. Cell Cycle. 2010; 9:4518-4524. [PubMed]
  • 134. Cheng Y, Yang J, Agarwal R, Green GM, Mease RC, Pomper MG, Meltzer SJ, Abraham JM. Strong inhibition of xenografted tumor growth by low-level doses of [(32)P]ATP. Oncotarget. 2011; 2:461-466. [PubMed]
  • 135. Guo C, Gasparian AV, Zhuang Z, Bosykh DA, Komar AA, Gudkov AV, Gurova KV. 9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-kappaB and p53 pathways. Oncogene. 2009; 28:1151-1161. [PubMed]
  • 136. Jani TS, DeVecchio J, Mazumdar T, Agyeman A, Houghton JA. Inhibition of NF-kappaB signaling by quinacrine is cytotoxic to human colon carcinoma cell lines and is synergistic in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or oxaliplatin. J Biol Chem. 2010; 285:19162-19172. [PubMed]
  • 137. Gurova K. New hopes from old drugs: revisiting DNA-binding small molecules as anticancer agents. Future Oncol. 2009; 5:1685-1704. [PubMed]
  • 138. Neznanov N, Komarov AP, Neznanova L, Stanhope-Baker P, Gudkov AV. Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib. Oncotarget. 2011; 2:209-221. [PubMed]
  • 139. Fasullo M, Burch AD, Britton A. Hypoxia enhances the replication of oncolytic herpes simplex virus in p53- breast cancer cells. Cell Cycle. 2009; 8:2194-2197. [PubMed]
  • 140. Wolf A, Agnihotri S, Guha A. Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget. 2010; 1:552-562. [PubMed]
  • 141. Zhao Y, Liu H, Liu Z, Ding Y, Ledoux SP, Wilson GL, Voellmy R, Lin Y, Lin W, Nahta R, Liu B, Fodstad O, Chen J, Wu Y, Price JE, Tan M. Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism. Cancer Res. 2011; 71:4585-4597. [PubMed]
  • 142. Tandon P, Gallo CA, Khatri S, Barger JF, Yepiskoposyan H, Plas DR. Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency. Proc Natl Acad Sci U S A. 2011; 108:2361-2365. [PubMed]
  • 143. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C, Guha A. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 2011; 208:313-326. [PubMed]
  • 144. Tennant DA, Duran RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer. 2010; 10:267-277. [PubMed]
  • 145. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A. 2010; 107:2037-2042. [PubMed]
  • 146. Dedes KJ, Wilkerson PM, Wetterskog D, Weigelt B, Ashworth A, Reis-Filho JS. Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations. Cell Cycle. 2011; 10:1192-1199. [PubMed]
  • 147. Rehman FL, Lord CJ, Ashworth A. Synthetic lethal approaches to breast cancer therapy. Nat Rev Clin Oncol. 2010; 7:718-724. [PubMed]
  • 148. Chan DA and Giaccia AJ. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov. 2011; 10:351-364. [PubMed]
  • 149. Packer LM, Rana S, Hayward R, O'Hare T, Eide CA, Rebocho A, Heidorn S, Zabriskie MS, Niculescu-Duvaz I, Druker BJ, Springer C, Marais R. Nilotinib and MEK Inhibitors Induce Synthetic Lethality through Paradoxical Activation of RAF in Drug-Resistant Chronic Myeloid Leukemia. Cancer Cell. 2011;.
  • 150. Reinhardt HC, Jiang H, Hemann MT, Yaffe MB. Exploiting synthetic lethal interactions for targeted cancer therapy. Cell Cycle. 2009; 8:3112-3119. [PubMed]
  • 151. Searle JS, Li B, Du W. Targeting Rb mutant cancers by inactivating TSC2. Oncotarget. 2010; 1:228-232. [PubMed]
  • 152. Li B, Gordon GM, Du CH, Xu J, Du W. Specific killing of Rb mutant cancer cells by inactivating TSC2. Cancer Cell. 2010; 17:469-480. [PubMed]
  • 153. Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci U S A. 2010; 107:9660-9664. [PubMed]
  • 154. Korotchkina LG, Leontieva OV, Bukreeva EI, Demidenko ZN, Gudkov AV, Blagosklonny MV. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging (Albany NY). 2010; 2:344-352. [PubMed]
  • 155. Leontieva OV, Gudkov AV, Blagosklonny MV. Weak p53 permits senescence during cell cycle arrest. Cell Cycle. 2010; 9:4323-4327. [PubMed]
  • 156. Leontieva OV and Blagosklonny MV. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY). 2010; 2:924-935. [PubMed]
  • 157. Blagosklonny MV and Hall MN. Growth and aging: a common molecular mechanism. Aging. 2009; 1:357-362. [PubMed]
  • 158. Blagosklonny MV. Rapamycin and quasi-programmed aging: Four years later. Cell Cycle. 2010; 9:1859-1862. [PubMed]
  • 159. Blagosklonny MV and Pardee AB. Exploiting cancer cell cycling for selective protection of normal cells. Cancer Res. 2001; 61:4301-4305. [PubMed]
  • 160. Rao B, van Leeuwen IM, Higgins M, Campbel J, Thompson AM, Lane DP, Lain S. Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy. Oncotarget. 2010; 1:639-650. [PubMed]
  • 161. Lane DP, Cheok CF, Lain S. p53-based cancer therapy. Cold Spring Harb Perspect Biol. 2010; 2:a001222 [PubMed]
  • 162. Choong ML, Yang H, Lee MA, Lane DP. Specific activation of the p53 pathway by low dose actinomycin D: a new route to p53 based cyclotherapy. Cell Cycle. 2009; 8:2810-2818. [PubMed]
  • 163. Apontes P, Leontieva OV, Demidenko ZN, Li F, Blagosklonny MV. Exploring long-term protection of normal human fibroblasts and epithelial cells from chemotherapy in cell culture. Oncotarget. 2011; 2:222-233. [PubMed]
  • 164. Gudkov AV and Komarova EA. Radioprotection: smart games with death. J Clin Invest. 2010; 120:2270-2273. [PubMed]
  • 165. Lee C and Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene. 2011; 30:3305-3316. [PubMed]
  • 166. Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle. 2010; 9:4474-4476. [PubMed]
  • 167. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, Redinbo MR. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010; 330:831-835. [PubMed]
  • 168. Kirsch DG, Santiago PM, di Tomaso E, Sullivan JM, Hou WS, Dayton T, Jeffords LB, Sodha P, Mercer KL, Cohen R, Takeuchi O, Korsmeyer SJ, Bronson RT, Kim CF, Haigis KM, Jain RK, et al. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science. 2010; 327:593-596. [PubMed]
  • 169. Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, Finkle D, Venook R, Wu X, Ridgway J, Schahin-Reed D, Dow GJ, Shelton A, Stawicki S, Watts RJ, Zhang J, et al. Therapeutic antibody targeting of individual Notch receptors. Nature. 2010; 464:1052-1057. [PubMed]
  • 170. McClelland SE, Burrell RA, Swanton C. Chromosomal instability: a composite phenotype that influences sensitivity to chemotherapy. Cell Cycle. 2009; 8:3262-3266. [PubMed]
  • 171. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009; 8:88-96. [PubMed]
  • 172. Algire C, Amrein L, Bazile M, David S, Zakikhani M, Pollak M. Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo. Oncogene. 2011; 30:1174-1182. [PubMed]
  • 173. Woodard J, Joshi S, Viollet B, Hay N, Platanias LC. AMPK as a therapeutic target in renal cell carcinoma. Cancer Biol Ther. 2010; 10:1168-1177. [PubMed]
  • 174. Martin-Castillo B, Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle. 2010; 9:1057-1064. [PubMed]
  • 175. Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Menendez JA. Metformin against TGFbeta-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle. 2010; 9:4461-4468. [PubMed]
  • 176. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells. Curr Mol Med. 2010; 10:674-691. [PubMed]
  • 177. He X, Esteva FJ, Ensor J, Hortobagyi GN, Lee MH, Yeung SC. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol. 2011;.
  • 178. Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila). 2010; 3:1060-1065. [PubMed]
  • 179. Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011; 71:4366-4372. [PubMed]
  • 180. Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 2011; 71:3196-3201. [PubMed]
  • 181. Anisimov VN. Metformin for aging and cancer prevention. Aging (Albany NY). 2010; 2:760-774. [PubMed]
  • 182. Liu B, Fan Z, Edgerton SM, Deng XS, Alimova IN, Lind SE, Thor AD. Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle. 2009; 8:2031-2040. [PubMed]
  • 183. Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, Thor AD. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 2009; 8:909-915. [PubMed]
  • 184. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle. 2010; 9:3807-3814. [PubMed]
  • 185. Birnbaum MJ and Shaw RJ. Genomics: Drugs, diabetes and cancer. Nature. 2011; 470:338-339. [PubMed]
  • 186. Zhang ZJ, Zheng ZJ, Kan H, Song Y, Cui W, Zhao G, Kip KE. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care. 2011; 34:2323-2328. [PubMed]
  • 187. Powe DG, Voss MJ, Zanker KS, Habashy HO, Green AR, Ellis IO, Entschladen F. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget. 2010; 1:628-638. [PubMed]
  • 188. Powe DG and Entschladen F. Targeted therapies: Using beta-blockers to inhibit breast cancer progression. Nat Rev Clin Oncol. 2011; 8:511-512. [PubMed]
  • 189. Schuller HM. Beta-adrenergic signaling, a novel target for cancer therapy? Oncotarget. 2010; 1:466-469. [PubMed]
  • 190. Melhem-Bertrandt A, Chavez-Macgregor M, Lei X, Brown EN, Lee RT, Meric-Bernstam F, Sood AK, Conzen SD, Hortobagyi GN, Gonzalez-Angulo AM. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol. 2011; 29:2645-2652. [PubMed]
  • 191. Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: a population- based study. J Clin Oncol. 2011; 29:2635-2644. [PubMed]
  • 192. Ganz PA and Cole SW. Expanding our therapeutic options: Beta blockers for breast cancer? J Clin Oncol. 2011; 29:2612-2616. [PubMed]
  • 193. Ateeq B, Tomlins SA, Chinnaiyan AM. AGTR1 as a therapeutic target in ER-positive and ERBB2-negative breast cancer cases. Cell Cycle. 2009; 8:3794-3795. [PubMed]