Related Experiment Video
Updated: Aug 12, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
The challenge of pathway and environment-mediated drug resistance
1Developmental Therapeutics Program, National Cancer Institute, Rockville, MD 20852, USA. sausville@nih.gov
Abstract:
New insights into cancer biology have allowed the definition of pathways critical to the success of the cancer cell. These include enhanced activity of positive regulators of cell proliferation, including oncogenes, and loss of tumor suppressor gene function; inactivation of cell death or enhancement of srvival functions; activation of telomerase, and enhanced ability of tumor cells to invade and reorganize host stroma. It follows then that these pathways may also mediate drug resistance, in a way that is fundamentally different from classically defined mechanisms for drug resistance which focus on altered handling of the drug or the drug's target by the resistant tumor cell. It is expected that resistance will occur that is predicated on altered pathway predominance in a tumor and altered tumor microenvironment. Cases which exemplify this possibility are presented, including up-regulation of angiogenesis-related regulators in relation to inhibition of EGF-related proliferative and angiogenesis-promoting functions. The implications of this thinking in relation to development of combination regimens targeting distinct pathways are considered.
Insights
Cancer cells utilize specific pathways for growth and survival, leading to drug resistance distinct from traditional mechanisms. Targeting these pathways and the tumor microenvironment offers new combination therapy strategies.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Oncology
Background:
- Cancer cells exhibit critical pathways for proliferation, survival, invasion, and telomerase activation.
- Tumor suppressor gene inactivation and oncogene activation are key to cancer cell success.
- Cancer drug resistance can arise from altered pathway activity and the tumor microenvironment.
Purpose of the Study:
- To explore novel mechanisms of cancer drug resistance.
- To investigate the role of critical cancer pathways in mediating drug resistance.
- To consider implications for developing combination cancer therapies.
Main Methods:
- Analysis of cancer biology pathways.
- Examination of tumor microenvironment influence on resistance.
- Case study review of angiogenesis and EGF pathway interactions.
Main Results:
- Cancer pathways, distinct from drug handling, mediate resistance.
- Altered pathway predominance and tumor microenvironment drive resistance.
- Up-regulation of angiogenesis regulators can occur with inhibition of EGF functions.
Conclusions:
- Cancer drug resistance is influenced by pathway activity and microenvironment.
- New therapeutic strategies should target distinct cancer pathways.
- Combination regimens offer a promising approach for overcoming resistance.
More Related Videos
08:59Looking 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
14:51Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Related Concept Videos
Treatment Resistant Cancers
Cellular Membranes and Drug Transport
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Development of Antibiotic Resistance