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Mechanisms of Resistance to Molecular Therapies Targeting the HGF/MET Axis

  • Simona Corso
  • Silvia Giordano
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 15)

Abstract

Targeted therapies by means of compounds that inhibit a specific target molecule represent a new perspective in the treatment of cancer. In contrast to conventional chemotherapy which acts mainly on dividing cells, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. The frequent alteration of receptor tyrosine kinases (RTKs) in human malignancies led them to be considered as targets for anti-neoplastic therapies; this resulted in the development of several inhibitors that showed a strong clinical activity. The concept of “oncogene addiction” has added a further rationale to the use of targeted therapies. In general, targeted therapies induce tumor regression in a good percentage of patients who are selected to express the target of the drug. However, almost invariably, responsive patients develop resistance to the treatment and undergo tumor relapse. A challenge associated with targeted therapies is, therefore, to predict mechanisms that could cause resistance to the treatment and to find ways to circumvent these hurdles.

The tyrosine kinase receptor for the Hepatocyte Growth Factor (HGF), encoded by the MET gene, has recently become a very interesting and studied target. This review will summarize the role of this oncogene in human tumor development, the strategies employed to achieve its inhibition and the mechanisms of resistance to MET-targeted therapies.

Keywords

MET-targeted therapies HGF/MET axis Resistance 

Abbreviations

EGFR

Epidermal growth factor receptor

FDA

Food and Drug Administration

FGFR2

Fibroblast growth factor receptor 2

HCC

Hepatocellular carcinoma

HGF

Hepatocyte growth factor

mAb

Monoclonal antibodies

MAPK

Mitogen-activated protein kinase

MNNG

Methylnitronitrosoguanidine

NSCLC

Non-small-cell lung carcinoma

PI3K

Phosphatidylinositide 3 kinase

RTK

Receptor tyrosine kinase

SF-RON

Short-form RON

TKI

Tyrosine kinase inhibitor

Notes

Conflict of Interest

No potential conflicts of interest were disclosed.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OncologyUniversity of Torino School of Medicine, Candiolo Cancer Institute-FPO IRCCSTorinoItaly

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