Rational combinations of targeted cancer therapies: background, advances and challenges
Haojie Jin1, Liqin Wang2, René Bernards3,4
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. hjjin1986@126.com.
Abstract:
Over the past two decades, elucidation of the genetic defects that underlie cancer has resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be highly effective, resistance to single-agent therapies remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. Here, we discuss the mechanisms of resistance to targeted therapies and how effective drug combinations can be identified to combat resistance. The challenges in clinically developing these combinations and future perspectives are considered.
Insights
Targeted cancer drugs are effective but lead to resistance. Understanding resistance mechanisms can guide rational drug combinations to improve cancer treatment outcomes.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Genetic defects in cancer have led to targeted therapies.
- Resistance to single-agent targeted therapies is a significant clinical challenge.
- Developing effective drug combinations is crucial but limited by clinical testing capacity.
Purpose of the Study:
- To discuss mechanisms of resistance to targeted cancer therapies.
- To explore strategies for identifying rational drug combinations to overcome resistance.
- To consider challenges and future perspectives in clinical development of combination therapies.
Main Methods:
- Review of mechanisms of targeted therapy resistance.
- Discussion of strategies for rational drug combination discovery.
- Analysis of clinical development challenges for combination therapies.
Main Results:
- Elucidation of genetic defects has yielded novel targeted cancer drugs.
- Resistance to single-agent therapies is a major hurdle.
- Rational drug combinations offer a promising approach to combat resistance.
Conclusions:
- Understanding molecular mechanisms of resistance is key to developing effective drug combinations.
- Careful selection of drug combinations can overcome therapy resistance.
- Further research and clinical development are needed for combination therapies.
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