학술논문
Playing the Devil's Advocate: Should We Give a Second Chance to mTOR Inhibition in Renal Clear Cell Carcinoma?--ie Strategies to Revert Resistance to mTOR Inhibitors
Document Type
Academic Journal
Author
Source
Cancer Management and Research. October 31, 2021, Vol. 13, p7623, 14 p.
Subject
Language
English
ISSN
1179-1322
Abstract
Introduction The treatment of metastatic Renal Cell Carcinoma (mRCC) has improved drastically over the last two decades. In fact, from a scarcity of specific therapeutic options, we assisted to the [...]
In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician's expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs. Keywords: everolimus, temsirolimus, Rapa-Link, anti-angiogenics, autophagy
In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician's expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs. Keywords: everolimus, temsirolimus, Rapa-Link, anti-angiogenics, autophagy