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Exploiting the therapeutic potential of the PI3K-AKT-mTOR pathway in enriched populations of gynecologic malignancies

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References

  • Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29
  • Obel JC, Friberg G, Fleming GF. Chemotherapy in endometrial cancer. Clin Adv Hematol Oncol 2006;4:459-68
  • Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev Anticancer Ther 2009;9:905-16
  • Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol 29:2259-65
  • Kong D, Suzuki A, Zou TT, et al. PTEN1 is frequently mutated in primary endometrial carcinomas. Nat Genet 1997;17:143-4
  • Mountzios G, Pectasides D, Bournakis E, et al. Developments in the systemic treatment of endometrial cancer. Crit Rev Oncol Hematol 2011;79:278-92
  • Shoji K, Oda K, Kashiyama T, et al. Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas. PLoS One 2012;7:e37431
  • Oda K, Stokoe D, Taketani Y, McCormick F. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 2005;65:10669-73
  • Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501
  • Diaz-Padilla I, Duran I, Clarke BA, Oza AM. Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer. Cancer Treat Rev 2012;38:767-75
  • Wang LE, Ma H, Hale KS, et al. Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to endometrial cancer and clinical outcomes. J Cancer Res Clin Oncol 2012;138:377-85
  • Lee DF, Hung MC. All roads lead to mTOR: integrating inflammation and tumor angiogenesis. Cell Cycle 2007;6:3011-14
  • Liu D, Hou P, Liu Z, et al. Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. Cancer Res 2009;69:7311-19
  • Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nature reviews Drug discovery 2009;8:627-44
  • Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 2002;8:128-35
  • Tewari KS, Monk BJ. American Society of Clinical Oncology 2011 Annual Meeting update: summary of selected gynecologic cancer abstracts. Gynecol Oncol 2011;122:209-12
  • Colombo N, McMeekin S, Schwartz P, et al. A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer. J Clin Oncol 2007;25:5516
  • Oza AM, Poveda A, Clamp AR, et al. A randomized phase II (RP2) trial of ridaforolimus (R) compared with progestin (P) or chemotherapy (C) in female adult patients with advanced endometrial carcinoma. J Clin Oncol 2011;29(Suppl; abstr 5009)
  • Demetri GD, Chawla SP, Ray-Coquard I, et al. Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol 2013;31:2485-92
  • Mackay H, Welch S, Tsao MS, et al. Phase II study of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer: NCIC CTG IND 192. J Clin Oncol 2011;29(Suppl; abstr 5013)
  • Oza AM, Elit L, Tsao MS, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol 2011;29:3278-85
  • Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81
  • Rini BI. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res 2008;14:1286-90
  • Thigpen JT, Brady MF, Alvarez RD, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 1999;17:1736-44
  • Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-9
  • Beeram M, Tan QT, Tekmal RR, et al. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol 2007;18:1323-8
  • Fleming GF, Filiaci VL, Hanjani P, et al. Gynecologic Oncology Group. Hormone therapy plus temsirolimus for endometrial carcinoma (EC): gynecologic oncology group trial #248. J Clin Oncol 2011;29
  • Fleming GF, Filiaci VL, Marzullo B, et al. Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study. Gynecol Oncol 2014;132:585-92
  • Slomovitz BM, Lu KH, Johnston T, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer 2010;116:5415-19
  • Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364:514-23
  • Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 2010;363:1801-11
  • Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56
  • Temkin SM, Yamada SD, Fleming GF. A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecol Oncol 2010;117:473-6
  • Shafer A, Zhou C, Gehrig PA, et al. Rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and induction of apoptosis. Int J Cancer 2010;126:1144-54
  • Campone M, Levy V, Bourbouloux E, et al. Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours. Br J Cancer 2009;100:315-21
  • Bae-Jump VL, Zhou C, Boggess JF, Gehrig PA. Synergistic effect of rapamycin and cisplatin in endometrial cancer cells. Cancer 2009;115:3887-96
  • Kollmannsberger C, Hirte H, Siu LL, et al. Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179). Ann Oncol 2012;23:238-44
  • Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol 2011;29:2259-65
  • Moroney JW, Schlumbrecht MP, Helgason T, et al. A phase I trial of liposomal doxorubicin, bevacizumab, and temsirolimus in patients with advanced gynecologic and breast malignancies. Clin Cancer Res 2011;17:6840-6
  • Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008;27:5497-510
  • Patnaik A, Appleman LJ, Mountz JM, et al. A first-in-human phase I study of intravenous PI3K inhibitor BAY 80-6946 in patients with advanced solid tumors: results of dose-escalation phase. J Clin Oncol 2011;29(Suppl; abstr 3035)
  • Lotze MT, Appleman LJ, Ramanathan RK, et al. Phase I study of intravenous PI3K inhibitor BAY 80-6946: Activity in patients (pts) with advanced solid tumors and non-Hodgkin lymphoma treated in MTD expansion cohorts. J Clin Oncol 2012;30(Suppl; abstr 3019)
  • Mazzoletti M, Bortolin F, Brunelli L, et al. Combination of PI3K/mTOR inhibitors: antitumor activity and molecular correlates. Cancer Res 2011;71:4573-84
  • Hirai H, Sootome H, Nakatsuru Y, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 2010;9:1956-67
  • Akt inhibitor mk2206 in treating patients with recurrent or advanced endometrial cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01307631&Search=Search
  • Brugarolas J. Renal-cell carcinoma–molecular pathways and therapies. N Engl J Med 2007;356:185-7
  • Friedenreich CM, Biel RK, Lau DC, et al. Case-control study of the metabolic syndrome and metabolic risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev 2011;20:2384-95
  • Friberg E, Orsini N, Mantzoros CS, Wolk A. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007;50:1365-74
  • Friberg E, Mantzoros CS, Wolk A. Diabetes and risk of endometrial cancer: a population-based prospective cohort study. Cancer Epidemiol Biomarkers Prev 2007;16:276-80
  • Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27:3822-9
  • Rodriguez-Pascual J, Cheng E, Maroto P, Duran I. Emergent toxicities associated with the use of mTOR inhibitors in patients with advanced renal carcinoma. Anticancer Drugs 2010;21:478-86
  • Bellmunt J, Szczylik C, Feingold J, et al. Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Oncol 2008;19:1387-92
  • Maroto JP, Hudes G, Dutcher JP, et al. Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus. J Clin Oncol 2011;29:1750-6
  • Duran I, Siu LL, Oza AM, et al. Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Eur J Cancer 2006;42:1875-80
  • Poole CD, Halcox JP, Jenkins-Jones S, et al. Omega-3 fatty acids and mortality outcome in patients with and without type 2 diabetes after myocardial infarction: a retrospective, matched-cohort study. Clin Ther 2013;35:40-51
  • Currie CJ, Poole CD, Jenkins-Jones S, et al. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 2012;35:299-304
  • Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009;32:1620-5
  • Evans JM, Donnelly LA, Emslie-Smith AM, et al. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-5
  • Chia VM, Newcomb PA, Trentham-Dietz A, Hampton JM. Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis. Int J Gynecol Cancer 2007;17:441-6
  • Cantrell LA, Zhou C, Mendivil A, et al. Metformin is a potent inhibitor of endometrial cancer cell proliferation–implications for a novel treatment strategy. Gynecol Oncol 2010;116:92-8
  • Paclitaxel and carboplatin with or without metformin hydrochloride in treating patients with stage III, IV, or recurrent endometrial cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT02065687&Search=Search
  • MacKenzie MJ, Ernst S, Johnson C, Winquist E. A phase I study of temsirolimus and metformin in advanced solid tumours. Invest New Drugs 2012;30:647-52
  • Molinolo AA, Marsh C, El Dinali M, et al. mTOR as a molecular target in HPV-associated oral and cervical squamous carcinomas. Clin Cancer Res 2012;18:2558-68
  • Janku F, Wheler JJ, Westin SN, et al. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol 2012;30:777-82
  • Temkin SM, Yamada SD, Fleming GF. A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecol Oncol 2010;117:473-6
  • Tinker AV, Ellard S, Welch S, et al. Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199). Gynecol Oncol 2013;180:269-74
  • Tan DS, Kaye S. Ovarian clear cell adenocarcinoma: a continuing enigma. J Clin Pathol 2007;60:355-60
  • Zorn KK, Bonome T, Gangi L, et al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 2005;11:6422-30
  • Mackay HJ, Brady MF, Oza AM, et al. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer 2010;20:945-52
  • Temsirolimus, carboplatin, and paclitaxel as first-line therapy in treating patients with newly diagnosed stage iii-iv clear cell ovarian cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01196429&Search=Search
  • A study of GDC-0980 in the treatment of recurrent or persistent endometrial carcinoma. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01455493&Search=Search
  • A study of two dual PI3K/mTOR inhibitors, PF-04691502 and PF-05212384 In patients with recurrent endometrial cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01420081&Search=Search
  • Safety and tolerability of DS-7423 in subjects with advanced solid malignant tumors. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01364844+&Search=Search
  • A study of BEZ235 in adult japanese patients with advanced solid tumors. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01195376&Search=Search

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