Biological insights into effective and antagonistic combinations of targeted agents with chemotherapy in solid tumors
Alberto Ocaña1, Orit Freedman, Eitan Amir
1Medical Oncology Department, Albacete University Hospital and AECC Unit, Albacete, Spain, albertoo@sescam.jccm.es.
Abstract:
The potential for synergistic interactions between anticancer drugs has been used to justify combinations of agents in clinical trials. However, most combinations of targeted agents and chemotherapies have been tested in the clinic without previous systematic evaluation of their potential benefit. Preclinical studies may help in the identification of synergistic or antagonistic interactions. For antineoplastic therapies, these studies may reveal synergy or antagonism of the drug combinations. Synergy occurs when two agents given together produce higher antitumoral activity than the sum of each individual drug. This represents the ideal setting for the development of combinations of targeted agents and chemotherapies. On the other side, certain drug combinations have shown adverse results, indicative of an antagonistic effect. In this article, we review the preclinical molecular bases that justify approved combinations of targeted agents with chemotherapy including examples of synergistic and antagonistic combinations. We also discuss scenarios for rational associations of targeted agents based on biological data and propose strategies that may improve the success of combinations of anticancer agents.
Insights
Combining targeted anticancer agents with chemotherapy requires careful preclinical evaluation. Understanding drug interactions, like synergy or antagonism, is crucial for developing effective combination therapies and improving patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Combination therapy is a cornerstone of cancer treatment, aiming for synergistic effects.
- Many targeted agent and chemotherapy combinations lack thorough preclinical evaluation of their interactions.
- Identifying synergistic or antagonistic drug effects is critical for optimizing antineoplastic therapies.
Purpose of the Study:
- To review the preclinical molecular basis of approved targeted agent-chemotherapy combinations.
- To highlight examples of both synergistic and antagonistic drug interactions.
- To propose strategies for rational drug associations and improved combination therapy success.
Main Methods:
- Review of preclinical studies on drug interactions in cancer therapy.
- Analysis of molecular mechanisms underlying synergistic and antagonistic effects.
- Discussion of biological data to guide rational combination strategies.
Main Results:
- Preclinical studies are essential for identifying synergistic or antagonistic interactions between anticancer agents.
- Synergy, where combined drugs yield greater activity than the sum of individual effects, is the goal for combination therapy.
- Antagonistic effects can lead to adverse outcomes, underscoring the need for careful evaluation.
Conclusions:
- Systematic preclinical evaluation of drug interactions is vital before clinical application of combination therapies.
- Understanding molecular bases of synergy and antagonism informs the rational design of targeted agent and chemotherapy combinations.
- Developing improved strategies for combining anticancer agents can enhance therapeutic efficacy and patient benefit.
Related Concept Videos
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...
02:50Combination Therapies and Personalized Medicine
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:27Tumor Immunotherapy