Mammalian Target of Rapamycin Inhibitors Resistance Mechanisms in Clear Cell Renal Cell Carcinoma

Current Signal Transduction Therapy
Anna KornakiewiczAnna M Czarnecka

Abstract

Mammalian target of rapamycin (mTOR) is a kinase protein involved in PI3K/AKT signaling with a central role in the processes of cell growth, survival and angiogenesis. Frequent mutations of this pathway make upstream and downstream components novel targets for tailored therapy design. Two mTOR inhibitors - everolimus and temsirolimus - enable an increase in overall survival (OS) or progression-free survival (PFS) time in a treatment of renal cancer. Despite recent advances in renal cancer treatment, resistance to targeted therapy is common. Understanding of molecular mechanisms is the basis of drug resistance which can facilitate prediction of success or failure in combinational or sequential targeted therapy. The article provides current knowledge on the mTOR signaling network and gives insight into the mechanisms of resistance to mTOR inhibitors from the complex perspective of RCC biology. The mechanisms of resistance developed not only by cancer cells, but also by interactions with tumor microenvironment are analyzed to emphasize the role of angiogenesis in ccRCC pathogenesis. As recent studies have shown the role of PI3K/AKT-mTOR pathway in proliferation and differentiation of cancer stem cells, we discuss cancer stem cell ...Continue Reading

Citations

Apr 24, 2016·Angiogenesis·Mary E ZieglerChristopher C W Hughes
Nov 4, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li-Xia XieXiao-Qun Ye
Oct 14, 2016·Frontiers in Pharmacology·Carmine D'AnielloSabrina Rossetti
Apr 2, 2016·International Journal of Oncology·Anna M CzarneckaCezary Szczylik
Jun 26, 2018·Frontiers in Oncology·Florinda Meléndez-RodríguezJulian Aragones
Aug 31, 2018·Cell Death & Disease·Ke HuiKaijie Wu
Feb 12, 2020·Journal of Experimental & Clinical Cancer Research : CR·Ninadh M D'CostaAlan I So
Aug 4, 2018·Indian Journal of Clinical Biochemistry : IJCB·Aman KumarRajendra Prasad
Jan 11, 2020·Frontiers in Oncology·Carmine D'AnielloGaetano Facchini
Jul 4, 2018·Molecular Cancer Therapeutics·Peter MakhovVladimir M Kolenko

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts

Related Concepts

Related Feeds

Adenocarcinoma, Clear Cell

Clear Cell Adenocarcinoma is a tumor that arises in the female genital tract and is characterized by cells that appear clear under the microscope. Discover the latest research here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Related Papers

Hematology/oncology Clinics of North America
Martin H VossRobert J Motzer
Expert Opinion on Investigational Drugs
Angelica Fasolo, Cristiana Sessa
© 2021 Meta ULC. All rights reserved