Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Treatment Resistant Cancers

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...

The Tumor Microenvironment

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...

The Tumor Microenvironment

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...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Targeted Cancer Therapies

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 specific...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Quantitative molecular cartography of emergency myelopoiesis reveals conserved modules of hematopoietic activation.

Cell stem cell·2026

Same author

Checkpoint blockade and the stem-like T cell trade-off.

Molecular oncology·2026

Same author

Cancer ecosystems: A dynamic interplay across scales.

Cell·2026

Same author

Glutamine addiction is a therapeutic target to block emergency myelopoiesis.

bioRxiv : the preprint server for biology·2026

Same author

Insights into a long life without cancer: The case of the bowhead whale.

Molecular oncology·2026

Same author

Tumor-derived aminopeptidase N promotes early stages of brain metastatic colonization.

Cell reports·2026

Search research articles

Related Experiment Video

Updated: May 19, 2026

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

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

Microenvironment-mediated resistance to anticancer therapies.

Oakley C Olson¹, Johanna A Joyce

¹Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

|September 5, 2012

Summary

Tumor cells can develop resistance to targeted therapies through genomic changes. However, external factors like HGF from the tumor microenvironment can also drive resistance to BRAF and HER2 inhibitors.

More Related Videos

Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation

Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation

Published on: September 19, 2019

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Related Experiment Videos

Last Updated: May 19, 2026

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

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

Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation

Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation

Published on: September 19, 2019

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Area of Science:

Oncology
Molecular Biology
Cancer Research

Background:

Resistance to molecularly targeted therapies is a significant clinical challenge.
Genomic alterations within tumor cells are known to cause resistance by reactivating oncogenic signaling pathways.
Tumor cell-extrinsic mechanisms of resistance are less understood.

Purpose of the Study:

To investigate the role of tumor microenvironment in mediating resistance to targeted therapies.
To identify soluble factors involved in paracrine resistance mechanisms.

Main Methods:

Review of recent studies identifying HGF as a resistance mediator.
Analysis of paracrine signaling pathways involved in targeted therapy resistance.

Main Results:

HGF (hepatocyte growth factor) has been identified as a key soluble factor.
HGF mediates resistance to BRAF and HER2 inhibitors.
Resistance is mediated in a paracrine manner, involving cell-to-cell communication.

Conclusions:

The tumor microenvironment plays a crucial role in acquired resistance to targeted therapies.
HGF signaling represents a potential therapeutic target to overcome resistance.
Understanding extrinsic resistance mechanisms is vital for improving cancer treatment strategies.