Related Experiment Video

Updated: Apr 25, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

10.8K

AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs

Catherine Wilson1, Xiaofen Ye1, Thinh Pham2

  • 1Department of Discovery Oncology, Genentech, South San Francisco, California.

Cancer Research
|August 16, 2014
PubMed

Insights

Targeting AXL receptor with small molecules offers a new strategy to overcome cancer drug resistance. Combining AXL inhibitors with antimitotic agents shows promise for treating mesenchymal tumors resistant to tyrosine kinase inhibitors (TKIs).

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Molecularly targeted therapies have transformed cancer treatment but face limitations due to acquired drug resistance.
  • Epithelial-to-mesenchymal transition (EMT) is a key mechanism conferring resistance to tyrosine kinase inhibitors (TKIs).
  • AXL receptor tyrosine kinase is associated with EMT and implicated in drug resistance, making it a potential therapeutic target.

Purpose of the Study:

  • To investigate the role of AXL in acquired TKI resistance in cancer.
  • To identify novel therapeutic strategies to overcome EMT-mediated drug resistance.

Main Methods:

  • Analysis of AXL expression across 643 human cancer cell lines.
  • Screening of small-molecule inhibitors for synergistic effects with AXL inhibition.
  • Evaluation of AXL inhibition combined with antimitotic agents in EMT-resistant cancer cells.

Main Results:

  • Elevated AXL expression strongly correlated with a mesenchymal phenotype in various cancers, notably triple-negative breast and non-small cell lung cancer.
  • AXL inhibition demonstrated specific synergy with antimitotic agents in eliminating EMT-driven, TKI-resistant cancer cells.
  • AXL inhibition alone did not fully restore sensitivity to EGFR TKIs in EMT-resistant cells.

Conclusions:

  • AXL is a significant marker of mesenchymal phenotype and TKI resistance in cancer.
  • A novel cotreatment strategy involving AXL inhibition and antimitotic agents can overcome treatment refractoriness in mesenchymal tumors.
  • This approach offers a promising avenue for managing difficult-to-treat, resistant cancers.

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

13.4K
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

3.4K

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...
7.0K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.2K
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...
4.9K
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...
6.3K
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...
2.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K