Related Experiment Video

Updated: Jan 6, 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

7.5K

Exploring and bypassing resistance to targeted therapies in colorectal cancer

Solène Favier1, Wei Xiong2, Mounira Chalabi-Dchar2

  • 1Université Claude Bernard Lyon 1, INSERM U-1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon 69008, France.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|November 12, 2025
PubMed

Insights

Colorectal cancer (CRC) therapies face resistance from genetic and environmental factors. This review explores innovative strategies like combination therapies and targeting persister cells to overcome resistance and improve patient outcomes.

Area of Science:

  • Oncology
  • Cancer Research
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a major global health concern, with targeted therapies offering improved outcomes.
  • Therapy resistance remains a significant challenge in CRC treatment, leading to disease progression.
  • Mechanisms of resistance include genetic mutations, epigenetic alterations, and tumor microenvironment (TME) adaptations.

Purpose of the Study:

  • To review recent breakthroughs and innovative strategies for overcoming therapeutic resistance in colorectal cancer.
  • To highlight the importance of understanding tumor heterogeneity, exosome communication, and the TME in addressing resistance.
  • To provide a roadmap for future research and clinical interventions aimed at improving CRC patient outcomes.

Main Methods:

  • Literature review of recent advancements in colorectal cancer research.
  • Analysis of emerging strategies targeting resistance mechanisms.
  • Synthesis of information on tumor biology, signaling pathways, and therapeutic approaches.

Main Results:

  • Tumor heterogeneity, exosome-mediated communication, and TME dynamics are key factors in CRC resistance.
  • Biomarker-guided combination therapies and epigenetic modulators show promise in restoring treatment efficacy.
  • Targeting cancer persister cells, cell cycle dysregulation, and DNA damage repair (DDR) pathways offers new avenues for durable responses.

Conclusions:

  • A comprehensive understanding of resistance mechanisms is crucial for developing effective CRC treatments.
  • Innovative strategies, including combination therapies and targeting persister cells, are essential for overcoming resistance.
  • Future research should focus on translating these findings into improved clinical outcomes for CRC patients.
Keywords:
Antibody-drug conjugates (ADC)Colorectal cancerCombination therapyDrug-tolerant persister cells (DTP)Precision oncologyTargeted therapy

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.3K
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

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

Published on: December 9, 2015

11.1K

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...
3.7K
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...
8.6K
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...
5.8K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
Adaptive Mechanisms in Cancer Cells02:53

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,...
6.8K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
9.9K