Related Experiment Video

Updated: Mar 2, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

PIK3CA hotspot mutations differentially impact responses to MET targeting in MET-driven and non-driven preclinical

Lluís Nisa1,2,3, Pascal Häfliger4, Michaela Poliaková5,6

  • 1Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, 3008, Bern, Switzerland. lluis.nisa@dkf.unibe.ch.

Molecular Cancer
|May 24, 2017
PubMed
Abstract

Insights

Activating PIK3CA mutations confer resistance to MET inhibitors in cancer. Combining PI3K and MET inhibitors overcomes this resistance, showing enhanced anti-tumor effects in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The MET receptor tyrosine kinase is a key target in cancer therapy.
  • Activating mutations in PIK3CA are prevalent in various cancers and can cause resistance to MET-targeted treatments.

Purpose of the Study:

  • To investigate the role of PIK3CA mutations in resistance to MET inhibition.
  • To evaluate the efficacy of combined MET and PI3K pathway inhibition in overcoming this resistance.

Main Methods:

  • Assessed MET and/or PI3K pathway inhibition in cell models with MET-activating mutations and PIK3CA mutations (E545K, H1047R).
  • Evaluated endpoints including PI3K pathway activation, cell proliferation, colony formation, cell death, wound healing, and an in vivo tumor model.
  • Utilized head and neck cancer cells with endogenous PIK3CA mutations.

Main Results:

  • PIK3CA mutations (E545K and H1047R) conferred resistance to MET inhibition in MET-driven cancer models.
  • PIK3CA H1047R demonstrated greater resistance induction than E545K.
  • Combined MET and PI3K inhibition synergistically overcame resistance and enhanced anti-tumor activity in vivo, particularly in tumors with PIK3CA H1047R mutations. Effects were more than additive in head and neck cancer cells.

Conclusions:

  • PIK3CA mutations are a significant mechanism of resistance to MET inhibitors.
  • Combination therapy targeting both PI3K and MET pathways holds promise for treating cancers with aberrant MET expression and PIK3CA mutations.
Keywords:
Head and neck cancerMET receptor tyrosine kinasePI3K pathwayPIK3CA mutationsResistance mechanisms

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.5K
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

25.2K

Related Concept Videos

Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
6.6K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.6K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
2.1K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K