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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
- Source :
- Cancer Management and Research
- Publication Year :
- 2021
- Publisher :
- Informa UK Limited, 2021.
-
Abstract
- 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.
- Subjects :
- Oncology
Renal clear cell carcinoma
autophagy
medicine.medical_specialty
Everolimus
biology
business.industry
Autophagy
anti-angiogenics
Review
everolimus
Discovery and development of mTOR inhibitors
Temsirolimus
Clinical trial
Rapa-Link
Internal medicine
temsirolimus
medicine
biology.protein
business
Mechanistic target of rapamycin
PI3K/AKT/mTOR pathway
medicine.drug
Subjects
Details
- ISSN :
- 11791322
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Cancer Management and Research
- Accession number :
- edsair.doi.dedup.....c0c6338df79a652c64c6e49638b7bbc5