Erstellt am 27 Jan 2020 17:33
Zuletzt geändert: 28 Jan 2020 17:30
Literatur:
- Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Kolorektales Karzinom, Langversion 2.1, 2019, AWMF Registrierungsnummer: 021/007OL, http://www.leitlinienprogramm-onkologie.de/leitlinien/kolorektales-karzinom/ [abgerufen am: 27.01.2020].
- Bhagwat SV, Gokhale PC, Crew AP, et al. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011 Aug;10(8):1394-406.
- Bahrami A, Khazaei M, Hasanzadeh M, et al. Therapeutic Potential of Targeting PI3K/AKT Pathway in Treatment of Colorectal Cancer: Rational and Progress. J Cell Biochem. 2018 Mar;119(3):2460-2469.
- Castellano D, Bajetta E, Panneerselvam A, et al. Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: A subgroup analysis of the phase III RADIANT-2 study. Oncologist. 2013;18(1):46-53.
- Hua H, Kong Q, Zhang H, et al. Targeting mTOR for cancer therapy. J Hematol Oncol. 2019 Jul 5;12(1):71.
"KRAS, BRAF, and TSC mutations are known as resistant markers for mTOR inhibitors, whereas PIK3CA mutations are sensitive marker … In general, most of mTOR inhibitors are well tolerated, while there are some common adverse effects including fatigue, rash, mucositis, and metabolic complications. mTOR inhibitors are associated with a significantly increased risk of hyperglycemia, hypertriglyceridemia, and hypercholesterolemia."
- Ng K, Tabernero J, Hwang J, et al. Phase II study of everolimus in patients with metastatic colorectal adenocarcinoma previously treated with bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Clin Cancer Res. 2013 Jul 15;19(14):3987-95.
- Reita D, Bour C, Benbrika R, et al. Synergistic Anti-Tumor Effect of mTOR Inhibitors with Irinotecan on Colon Cancer Cells. Cancers (Basel). 2019 Oct 17;11(10). pii: E1581.
"We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. … We showed that the AZD8055 and AZD2014 inhibitors were much more potent than rapamycin to reduce cell viability of four colon cell lines. On the other hand, whereas AZD2014 alone inhibits migration by 40%, the drug combination led to 70% inhibition. Similarly, neither irinotecan nor AZD2014 significantly reduced cell invasion, whereas a combination of the two inhibits invasion by 70%."
- Roper J, Richardson MP, Wang WV, et al. The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer. PLoS One. 2011;6(9):e25132.
- Spindler KL, Sorensen MM, Pallisgaard N, et al. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer: outcome and results of KRAS mutational analysis in plasma. Acta Oncol. 2013 Jun;52(5):963-70.
- Srivastava RK, Li C, Khan J, et al. Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells. Proc Natl Acad Sci U S A. 2019 Dec 3;116(49):24583-24592.
"Exposure to rapamycin, an mTORC1 inhibitor, or mTORC2 knockdown alone had little or reduced effect relative to the combination. … These data indicate a role of mTORC2 in regulating tumor growth by macropinocytosis and suggest that dual inhibitors could help block refractory or recurrent RMS and perhaps other neoplasms and other cancer as well."
- Temraz S, Mukherji D, Shamseddine A. Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers. Int J Mol Sci. 2015 Sep 23;16(9):22976-88.
"Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC."
- Tian T, Li X, Zhang J. mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy. Int J Mol Sci. 2019 Feb 11;20(3). pii: E755.
"Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need …"
- Wolpin BM, Ng K, Zhu AX, et al. Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Oncologist. 2013;18(4):377-8.
- Yeung Y, Lau DK, Chionh F, et al. K-Ras mutation and amplification status is predictive of resistance and high basal pAKT is predictive of sensitivity to everolimus in biliary tract cancer cell lines. Mol Oncol. 2017 Sep;11(9):1130-1142.
"K-Ras mutations and/or amplifications were identified in 45% of cell lines and were associated with resistance to everolimus. Activating mutations in PIK3CA or loss of PTEN was not predictive of everolimus response; …"
- Zhang Y, Zheng XF. mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors. Cell Cycle. 2012 Feb 1;11(3):594-603.
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