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Potential Successes and Challenges of Targeted Cancer Therapies
Dorothy M K Keefe1, Emma H Bateman1
1Mucositis Research Group, Discipline of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia.
Abstract:
The concept and realization of targeted anticancer therapy (TAT) have existed for at least two decades and continue to expand rapidly. It has become clear that there is no "magic bullet" to cure cancer and that even TATs are unlikely to be successful as single agents, necessitating combination with chemotherapy, radiotherapy, or even other targeting agents. The other promise that has not been fulfilled by TAT is that of reduced toxicity. It was thought that by targeting receptors on or within cells, rather than particular phases of the cell cycle, TATs would not be toxic. However, it turns out that the targets also exist on or within normal cells and that there is even cross-reactivity between receptors on nontarget tissues. All of this results in toxicity, the mechanism of which are the same as the mechanism of action of the drugs, making toxicity reduction or prevention very difficult. This leads to new toxicities with new targeted treatments. Nevertheless, all of the above should not detract from the obvious successes of targeted agents, which have turned several acutely fatal cancers into chronic diseases and rendered some hitherto untreatable cancers into treatable diseases.
Insights
Targeted anticancer therapies (TATs) show success in treating advanced cancers but often require combination treatments and can cause toxicity due to off-target effects. Further research is needed to optimize their use and manage side effects.
Area of Science:
- Oncology
- Pharmacology
Background:
- Targeted anticancer therapy (TAT) has been a focus in cancer treatment for over 20 years.
- Despite advancements, TATs are rarely effective as monotherapy and often necessitate combination with traditional treatments like chemotherapy or radiotherapy.
- The anticipated benefit of reduced toxicity with TATs has not been fully realized.
Purpose of the Study:
- To review the successes and limitations of targeted anticancer therapies.
- To discuss the mechanisms of toxicity associated with TATs.
- To highlight the ongoing challenges and future directions in targeted cancer treatment.
Main Methods:
- Review of existing literature on targeted anticancer therapies.
- Analysis of the mechanisms of action and toxicity of TATs.
- Evaluation of clinical outcomes and challenges in current TAT applications.
Main Results:
- TATs have transformed fatal cancers into chronic conditions and improved outcomes for previously untreatable cancers.
- Toxicity remains a significant issue, stemming from the presence of targets on normal cells and cross-reactivity.
- The mechanisms of drug action and toxicity are often intertwined, complicating toxicity management.
Conclusions:
- Targeted anticancer therapies offer significant clinical benefits but require combination strategies and careful toxicity management.
- Understanding and mitigating off-target effects are crucial for improving the safety and efficacy of TATs.
- Continued research is essential to overcome the challenges and fully harness the potential of targeted cancer treatments.
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