Related Experiment Video

Updated: May 15, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Gene expression profile identifies tyrosine kinase c-Met as a targetable mediator of antiangiogenic therapy

Arman Jahangiri1, Michael De Lay, Liane M Miller

  • 1Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94158, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 12, 2013
PubMed
Abstract

Insights

The study identified the receptor tyrosine kinase c-Met as a key mediator of glioblastoma resistance to antiangiogenic therapy. Targeting c-Met may overcome this resistance, improving treatment outcomes for glioblastoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
  • Antiangiogenic therapy, such as bevacizumab, shows initial efficacy but resistance often develops.
  • Understanding resistance mechanisms is crucial for improving GBM treatment strategies.

Purpose of the Study:

  • To identify molecular mediators driving resistance to antiangiogenic therapy in glioblastoma.
  • To investigate the therapeutic potential of targeting identified mediators in preclinical models.

Main Methods:

  • Microarray analysis of bevacizumab-resistant glioblastomas (BRG) compared to pretreatment tumors.
  • Establishment of novel xenograft models to study antiangiogenic therapy resistance.
  • Inhibition of c-Met using small molecule inhibitors and short hairpin RNA (shRNA).

Main Results:

  • Upregulation of receptor tyrosine kinase c-Met was identified in BRG compared to pretreatment tumors.
  • BRG exhibited increased hypoxia, correlating with c-Met upregulation and activation of downstream signaling pathways (FAK, STAT3).
  • Targeting c-Met with inhibitors or shRNA reversed bevacizumab resistance in xenograft models, inhibiting invasion and promoting sensitivity.

Conclusions:

  • c-Met plays a significant role in glioblastoma cell survival under hypoxia and invasion, contributing to antiangiogenic therapy resistance.
  • Targeting c-Met represents a promising strategy to overcome or prevent resistance to antiangiogenic therapies in glioblastoma.
  • These findings provide a rationale for clinical trials investigating c-Met inhibitors in combination with antiangiogenic agents for GBM treatment.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Related Concept Videos

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 specific...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...