In several tumors the PI3K/AKT/mTOR pathway is frequently disrupted, an event that results in uncontrolled cell proliferation and tumor growth. Through the years, several compounds have been developed to inhibit the pathway at different steps: the mammalian target of rapamycin (mTOR) seemed to be the most qualified target. However, this kinase has such a key role in cell survival that mechanisms of resistance are rapidly developed. Nevertheless, clinical results obtained with mTOR inhibitors in breast cancer, renal cell carcinoma, neuroendocrine tumors and mantle cell lymphoma push oncologists to actively further develop these drugs, maybe by better selecting the population to which they are offered, through the research of predictive factors of responsiveness. In this review, we aim to describe mechanisms of resistance to mTOR inhibitors, from preclinical and clinical perspectives.

Mechanisms of resistance to mTOR inhibitors

Bianco C.
2020-01-01

Abstract

In several tumors the PI3K/AKT/mTOR pathway is frequently disrupted, an event that results in uncontrolled cell proliferation and tumor growth. Through the years, several compounds have been developed to inhibit the pathway at different steps: the mammalian target of rapamycin (mTOR) seemed to be the most qualified target. However, this kinase has such a key role in cell survival that mechanisms of resistance are rapidly developed. Nevertheless, clinical results obtained with mTOR inhibitors in breast cancer, renal cell carcinoma, neuroendocrine tumors and mantle cell lymphoma push oncologists to actively further develop these drugs, maybe by better selecting the population to which they are offered, through the research of predictive factors of responsiveness. In this review, we aim to describe mechanisms of resistance to mTOR inhibitors, from preclinical and clinical perspectives.
2020
Mechanisms of resistance
mTOR inhibitors
Predictive factors
Adult
Antineoplastic Agents
Breast Neoplasms
Cell Proliferation
Drug Resistance, Neoplasm
Humans
Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Lymphoma, Mantle-Cell
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/62088
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