Related Experiment Video

Updated: Apr 4, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.7K

PTPN11 Is a Central Node in Intrinsic and Acquired Resistance to Targeted Cancer Drugs

Anirudh Prahallad1, Guus J J E Heynen1, Giovanni Germano2

  • 1Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.

Cell Reports
|September 15, 2015
PubMed

Insights

Targeting protein tyrosine phosphatase non-receptor type 11 (PTPN11) overcomes BRAF inhibitor resistance in colon cancer. PTPN11 suppression blocks receptor tyrosine kinase signaling, making cancer cells sensitive to targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • BRAF (V600E) mutant melanomas respond to BRAF inhibitors, but colon cancers with this mutation are resistant.
  • This resistance stems from feedback activation of the epidermal growth factor receptor (EGFR).

Purpose of the Study:

  • To identify phosphatases that, when suppressed, restore sensitivity to BRAF inhibitors in BRAF mutant colon cancer.
  • To explore PTPN11 as a potential drug target for overcoming resistance to targeted cancer therapies.

Main Methods:

  • RNA-interference-based genetic screen in BRAF mutant colon cancer cells.
  • Assessed sensitivity to BRAF inhibitors after phosphatase knockdown.
  • Investigated the downstream signaling effects of PTPN11 inhibition.

Main Results:

  • Suppression of protein tyrosine phosphatase non-receptor type 11 (PTPN11) confers sensitivity to BRAF inhibitors in colon cancer.
  • PTPN11 inhibition blocks signaling from receptor tyrosine kinases (RTKs) to the RAS-MEK-ERK pathway.
  • PTPN11 suppression is lethal to RTK-driven cells and prevents acquired resistance via RTK activation.

Conclusions:

  • PTPN11 is a viable drug target to overcome both intrinsic and acquired resistance to targeted cancer drugs.
  • Activated PTPN11 can serve as a biomarker for drug resistance mediated by RTK activation.

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.6K
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

1.3K

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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

1.8K
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K
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
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.3K
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