Related Experiment Video

Updated: Apr 1, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.3K

TAMing resistance to multi-targeted kinase inhibitors through Axl and Met inhibition

D J Pinato1, S Chowdhury2, J Stebbing1

  • 1Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.

Oncogene
|October 6, 2015
PubMed

Insights

The study reveals how Axl and Met activation drives resistance to sunitinib in renal cell carcinoma (RCC). This research supports developing Axl and Met inhibitors like cabozantinib for targeted therapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • TAM receptor tyrosine kinases (Axl) and Met are linked to cancer progression and metastasis.
  • Axl and Met are increasingly recognized as drivers of adaptive resistance to targeted cancer therapies.
  • Understanding resistance mechanisms is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To elucidate the mechanisms by which Axl and Met activation contribute to acquired resistance to sunitinib in renal cell carcinoma (RCC).
  • To provide a preclinical rationale for targeting Axl and Met in sunitinib-resistant RCC.

Main Methods:

  • The study by Zhou et al. investigated the molecular links between Axl and Met signaling pathways.
  • Preclinical models of sunitinib-resistant RCC were utilized to examine resistance mechanisms.
  • The research focused on the role of epithelial-to-mesenchymal transition in mediating resistance.

Main Results:

  • Axl and Met activation were identified as key mediators of acquired resistance to sunitinib in RCC.
  • The study demonstrated that these receptor tyrosine kinases promote cancer hallmarks like angiogenesis and invasion.
  • Upregulation of epithelial-to-mesenchymal transition was linked to Axl and Met-driven resistance.

Conclusions:

  • Axl and Met signaling pathways play a critical role in the development of resistance to sunitinib in RCC.
  • Targeting Axl and Met, potentially with inhibitors like cabozantinib, is a promising strategy for overcoming anti-angiogenic therapy resistance in RCC.
  • Further clinical investigation of Axl and Met inhibitors is warranted for patients with resistant RCC.

More Related Videos

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.4K
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

9.3K

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...
9.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.3K
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...
6.3K
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...
5.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.9K
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...
3.9K