Lessons Learned from Two Decades of Anticancer Drugs
Zhichao Liu1, Brian Delavan2, Ruth Roberts3
1National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Abstract:
Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena. The disappointing performance of investigational anticancer candidates implies that there are some shortcomings in the translation of preclinical in vitro and in vivo models to humans, and that heterogeneity in the patient population presents a significant challenge. Here, we summarize both successful and failed experiences in anticancer development during the past 20 years and help identify why the current paradigm may be suboptimal. We also offer potential strategies for improvement.
Insights
Anticancer drug development faces high failure rates due to translation issues from preclinical models and patient heterogeneity. This review examines past successes and failures to propose improved strategies for effective cancer drug discovery.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Anticancer drug development has evolved significantly over 20 years, shifting from cytotoxic agents to targeted and immune-based therapies.
- Over 200 anticancer drugs are now available, yet development remains high-risk with significant attrition in later clinical trial phases.
Purpose of the Study:
- To review successful and unsuccessful anticancer drug development experiences from the past two decades.
- To identify limitations in the current drug development paradigm.
- To propose strategies for enhancing the success rate of anticancer drug candidates.
Main Methods:
- Review of historical data on anticancer drug development.
- Analysis of attrition rates and reasons for failure in clinical trials.
- Synthesis of successful and failed case studies.
Main Results:
- Shortcomings in translating preclinical findings (in vitro and in vivo) to human patients contribute to high failure rates.
- Patient population heterogeneity poses a significant challenge in anticancer drug development.
- Current drug development paradigms may be suboptimal in addressing these translational and heterogeneity issues.
Conclusions:
- Despite advancements, anticancer drug development remains challenging due to translational gaps and patient variability.
- A critical evaluation of past development experiences is necessary to refine current strategies.
- Implementing improved strategies is crucial for increasing the success of future anticancer drug discovery and development.
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