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Published on: July 25, 2020
Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions
Matthew Rubinstein1, Madeline Lauren Hong1, Rishi Kumar Nanda1
1College of Osteopathic Medicine, Touro University, Henderson, NV 89014, USA.
Abstract:
The ever-expanding development of tissue-agnostic therapies which target malignancies based on specific mutations rather than tissue origin have transformed the landscape of oncology. The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. As the therapeutic arsenal continues to grow, it is crucial to understand how these therapies truly benefit patients and to address the barriers that stand in the way of making them more widely available. Although these therapies have shown effectiveness across multiple cancer types, substantial challenges persist, including overcoming the burden of intratumoral heterogeneity and resistance mechanisms that reduce therapeutic efficacy. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers.
Insights
Tissue-agnostic therapies, targeting cancer mutations regardless of origin, are revolutionizing oncology. Research is ongoing to maximize patient benefit and overcome challenges like tumor heterogeneity and resistance for broader access.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Tissue-agnostic therapies target specific mutations, not tumor location, transforming cancer treatment.
- These therapies represent a significant shift towards precision oncology, offering new hope for diverse patient populations.
Purpose of the Study:
- To review the impact, safety, and challenges of emerging tissue-agnostic therapies.
- To explore strategies for refining patient selection and improving access to biomarker testing.
- To highlight the role of pan-histological biomarkers in guiding treatment decisions.
Main Methods:
- Literature review of current tissue-agnostic therapies and clinical trials.
- Analysis of therapeutic efficacy, safety profiles, and resistance mechanisms.
- Discussion of biomarker development and patient selection strategies.
Main Results:
- Tissue-agnostic therapies show effectiveness across various cancer types, offering significant patient benefits.
- Challenges include intratumoral heterogeneity and acquired resistance, impacting long-term efficacy.
- Emerging biomarkers like neoantigen burden are crucial for patient stratification.
Conclusions:
- Tissue-agnostic therapies are a transformative advancement in precision oncology.
- Ongoing research is essential to optimize treatment strategies and overcome access barriers.
- Improving biomarker testing accessibility is key to realizing the full potential of these therapies.
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