Related Experiment Video

Updated: Jun 14, 2025

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
12:03

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

Published on: December 9, 2016

12.4K

MERTK Is a Potential Therapeutic Target in Ewing Sarcoma

Sherri K Smart1,2, Tsz Y Yeung1,2, M Olivia Santos3

  • 1Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Cancers
|August 29, 2024
PubMed

Insights

MER proto-oncogene tyrosine kinase (MERTK) is a promising target for Ewing sarcoma (EWS). Inhibiting MERTK with MRX-2843 shows potent anti-tumor activity and may improve outcomes for EWS patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Advanced or relapsed Ewing sarcoma (EWS) has poor outcomes and limited treatment options.
  • Current EWS treatments have significant side effects.
  • MER proto-oncogene tyrosine kinase (MERTK) is implicated in tumor cell survival and treatment resistance.

Purpose of the Study:

  • To investigate MERTK as a therapeutic target in EWS.
  • To evaluate the efficacy of MRX-2843, a MERTK inhibitor, in EWS models.
  • To explore combination therapies involving MRX-2843.

Main Methods:

  • Assessed MERTK expression in EWS cell lines and patient samples.
  • Utilized CRISPR-based library screens to determine MERTK dependency in EWS.
  • Treated EWS cells with MRX-2843 and evaluated MERTK signaling and cell viability.
  • Tested combination therapies with MRX-2843 and BCL-2 inhibitors (venetoclax, navitoclax).

Main Results:

  • MERTK was ubiquitously expressed in EWS cell lines and patient samples.
  • EWS cells demonstrated significant dependency on MERTK.
  • MRX-2843 potently inhibited MERTK signaling and exhibited strong anti-tumor activity (IC50: 178-297 nM).
  • Combined MRX-2843 and BCL-2 inhibitors showed enhanced therapeutic effects.

Conclusions:

  • MERTK is a viable therapeutic target for EWS.
  • MRX-2843 demonstrates significant anti-EWS activity.
  • Combination therapy with MRX-2843 and BCL-2 inhibitors warrants further investigation for EWS treatment.
Keywords:
BCL-2BCL-XLMERTKMRX-2843ewing sarcomasmall-molecule inhibitor

More Related Videos

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate07:31

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

Published on: May 3, 2021

3.6K
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

2.7K

Related Concept Videos

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...
6.4K
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...
7.5K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.4K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
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...
3.8K