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Published on: April 5, 2018
Progresses and Pitfalls of Epigenetics in Solid Tumors Clinical Trials
Alice Rossi1,2, Francesca Zacchi1,2, Anna Reni1
1Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University and Hospital Trust (AOUI) of Verona, 37134 Verona, Italy.
Abstract:
Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies.
Insights
Epigenetic drugs show promise in solid tumors, especially when combined with other cancer treatments. This review explores their evolution and future potential in precision medicine and combination therapies.
Area of Science:
- Oncology
- Epigenetics
- Pharmacology
Background:
- Epigenetic dysregulation is a key driver in cancer development and progression.
- Current epigenetic drugs are effective in hematological cancers but limited in solid tumors.
- Advances in drug development and cancer biology offer new opportunities for solid tumors.
Purpose of the Study:
- To review the evolution of epigenetic drugs from monotherapy to combination therapy.
- To evaluate the preclinical and clinical evidence for epigenetic drugs in solid tumors.
- To discuss strategies for optimizing combination therapy development.
Main Methods:
- Critical evaluation of the literature on epigenetic drug development.
- Analysis of preclinical data and completed/ongoing clinical trials.
- Exploration of trial design and drug scheduling for combination therapies.
Main Results:
- Epigenetic drugs are increasingly explored for solid tumor treatment via precision medicine.
- Significant potential exists for epigenetic drugs to synergize with chemotherapy, radiation, hormone therapy, targeted therapy, and immunotherapy.
- Optimized trial designs and scheduling are crucial for successful combination therapy development.
Conclusions:
- Epigenetic drugs are transitioning towards combination therapies for enhanced efficacy in solid tumors.
- Further research and strategic clinical trial design are needed to realize the full potential of epigenetic therapies.
- Combination approaches hold promise for overcoming resistance and improving patient outcomes in various cancers.
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