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Published on: July 25, 2020
Targeting molecular subtypes in solid cancers: successes and failures
Rita Assi1, Nuria Kotecki2, Ahmad Awada2
1Department of Internal Medicine, Division of Hematology-Oncology, Lebanese American University Medical Center, Rizk Hospital, Beyrouth, Lebanon.
Purpose Of Review:
We herein review some of the major patterns of resistance and lessons learned from the use of earlier targeted therapies in two genotype-driven solid tumors.
Recent Findings:
Targeted agents have rapidly expanded in the field of oncology over the past 2 decades. The breakthroughs achieved by these agents have been, however, hindered by the inevitable development of drug resistance. Intrinsic or acquired mechanisms of resistance eventually lead to treatment tolerance and tumoral plasticity with phenotypic switch and evasion of the original targeted pathway. Failures in such therapies also result from poor selectivity of the target, drug delivery, and unaffordable costs.
Summary:
Based on above findings, collaborative efforts are advancing at the molecular level to design better drugs or combinatorial strategies and to develop more sensitive assays to monitor responses and the emergence of resistance.
Insights
Drug resistance is a major challenge in targeted cancer therapies. Understanding resistance patterns is key to developing new strategies for solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Targeted therapies have revolutionized cancer treatment over the last two decades.
- The efficacy of targeted agents is often limited by the development of intrinsic or acquired drug resistance.
- Mechanisms of resistance include phenotypic switching, pathway evasion, poor drug selectivity, delivery issues, and high costs.
Purpose of the Study:
- To review major resistance patterns observed with earlier targeted therapies.
- To extract key lessons learned from the application of these therapies in solid tumors.
- To highlight the challenges hindering the success of targeted cancer treatments.
Main Methods:
- Review of existing literature on targeted therapies in solid tumors.
- Analysis of documented mechanisms of drug resistance.
- Identification of patterns in treatment failures.
Main Results:
- Drug resistance is an inevitable consequence of targeted therapy, involving complex molecular and cellular adaptive mechanisms.
- Tumor plasticity and phenotypic switching contribute significantly to acquired resistance.
- Failures are also attributed to factors beyond molecular resistance, including drug delivery and cost.
Conclusions:
- Collaborative efforts are underway to design improved targeted drugs and combination strategies.
- Development of sensitive assays is crucial for monitoring treatment response and detecting emerging resistance.
- Addressing resistance mechanisms is essential for advancing the clinical utility of targeted cancer therapies.
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