Highlights in Resistance Mechanism Pathways for Combination Therapy
João M A Delou1, Alana S O Souza1, Leonel C M Souza1
1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Abstract:
Combination chemotherapy has been a mainstay in cancer treatment for the last 60 years. Although the mechanisms of action and signaling pathways affected by most treatments with single antineoplastic agents might be relatively well understood, most combinations remain poorly understood. This review presents the most common alterations of signaling pathways in response to cytotoxic and targeted anticancer drug treatments, with a discussion of how the knowledge of signaling pathways might support and orient the development of innovative strategies for anticancer combination therapy. The ultimate goal is to highlight possible strategies of chemotherapy combinations based on the signaling pathways associated with the resistance mechanisms against anticancer drugs to maximize the selective induction of cancer cell death. We consider this review an extensive compilation of updated known information on chemotherapy resistance mechanisms to promote new combination therapies to be to discussed and tested.
Insights
This review explores how understanding cancer cell signaling pathways can improve combination chemotherapy. It aims to guide the development of novel anticancer drug combinations to overcome resistance and enhance cancer cell death.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Combination chemotherapy is a cornerstone of cancer treatment, yet its underlying mechanisms are often poorly understood.
- While single anticancer agents' pathways are known, most drug combinations lack clear mechanistic insights.
- Resistance to chemotherapy remains a significant challenge in cancer therapy.
Purpose of the Study:
- To review common signaling pathway alterations in response to cytotoxic and targeted anticancer drugs.
- To discuss how understanding signaling pathways can inform innovative combination therapy strategies.
- To highlight potential combination therapies based on resistance-associated signaling pathways to improve cancer cell death.
Main Methods:
- Literature review of signaling pathways affected by anticancer drugs.
- Analysis of resistance mechanisms in cancer cells.
- Compilation of updated information on chemotherapy resistance.
Main Results:
- Identified common signaling pathway alterations induced by various anticancer treatments.
- Detailed mechanisms of chemoresistance linked to specific signaling pathways.
- Provided a framework for developing rational drug combinations.
Conclusions:
- Knowledge of signaling pathways is crucial for designing effective anticancer combination therapies.
- Targeting resistance mechanisms through pathway-informed combinations can enhance treatment efficacy.
- This review compiles essential information to foster the development and testing of new combination strategies.
More Related Videos
Related Concept Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
05:01A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
02:50Combination Therapies and Personalized Medicine
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...
07:42Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
06:52Characterizing Herbivore Resistance Mechanisms: Spittlebugs on Brachiaria spp. as an Example
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms