Related Experiment Video

Updated: Dec 19, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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

9.1K

NRG1/ERBB3 Pathway Activation Induces Acquired Resistance to XPO1 Inhibitors

Takahito M Miyake1, Sunila Pradeep2, Emine Bayraktar1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Molecular Cancer Therapeutics
|June 6, 2020
PubMed

Insights

Selective inhibitors of nuclear export (SINE) resistance in ovarian cancer is linked to the NRG1/ERBB3 pathway. Targeting ERBB3 may overcome SINE resistance, suggesting NRG1 and ERBB3 as biomarkers for SINE therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Mechanisms of resistance to XPO1 inhibitors (SINE) in cancer are not fully understood.
  • Ovarian cancer cell lines resistant to SINE were developed to study adaptive resistance.

Purpose of the Study:

  • To investigate the mechanisms of adaptive resistance to SINE in ovarian cancer.
  • To identify potential biomarkers and therapeutic targets for overcoming SINE resistance.

Main Methods:

  • Established SINE-resistant ovarian cancer cell lines from in vivo mouse tumors.
  • Utilized protein and genomic arrays for pathway analysis.
  • Employed siRNA to deplete ERBB3 and assessed the impact of exogenous NRG1.

Main Results:

  • Upregulation of the Neuregulin 1 (NRG1)/Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3) pathway was identified in SINE-resistant cells.
  • ERBB3 depletion restored SINE's antitumor effects in vitro and in vivo.
  • Exogenous NRG1 reduced SINE's efficacy in an ERBB3-dependent manner.

Conclusions:

  • NRG1 and ERBB3 expression may serve as predictive biomarkers for SINE treatment response.
  • The NRG1/ERBB3 pathway is a relevant therapeutic target for overcoming SINE resistance in ovarian cancer.
  • Further clinical trials are warranted to evaluate NRG1 and ERBB3 as biomarkers and therapeutic targets.

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

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

7.5K
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

14.2K

Related Concept Videos

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...
3.6K
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...
7.6K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.2K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
444
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...
8.5K
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...
4.5K