Mutant -driven cancers depend on /SHP2 phosphatase

Journal: Nature Medicine

Published: 2018-05-28

DOI: 10.1038/s41591-018-0024-8

Affiliations: 6

Authors: 26

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Research Highlight

Combo drug strategy for cancer

© Thomas Northcut/Getty

© Thomas Northcut/Getty

Targeting a critical signalling protein called SHP2 may augment the anti-tumour effects of a promising class of approved drugs known as MEK inhibitors.

A team led by Technical University of Munich researchers studied mouse models of lung and pancreatic cancer driven by altered forms of KRAS, a gene found mutated in many patients with these tumour types.

When the researchers blocked the activity of SHP2, either by genetic or pharmacological means, they saw delays in cancer progression.

SHP2 inhibition helped reduce levels of the mutant KRAS protein, but the treatment alone was insufficient to induce tumour regression. Only by adding an additional MEK-targeted drug could the researchers achieve tumour shrinkage in the mouse models. The synergistic drug combination also cut the risk of tumours developing resistance to the MEK inhibitor.

The findings highlight a compelling dual-drug strategy that merits further testing in clinical trials.

Supported content

  1. Nature Medicine 24, 954–960 (2018). doi: 10.1038/s41591-018-0024-8
Institutions FC
TUM Department of Internal Medicine II (Gastroenterology), Germany 0.67
Max Delbrück Center for Molecular Medicine (MDC), Germany 0.12
Medicinal Chemistry Group, FMP, Germany 0.08
Center of Surgery, Uni Freiburg, Germany 0.06
School of Medicine, KU, Turkey 0.04
Institute of Biomedical Research Alberto Sols (IIBM), Spain 0.04

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