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Review
. 2023 Apr;40(4):1379-1392.
doi: 10.1007/s12325-022-02362-4. Epub 2022 Nov 23.

Histology-Agnostic Drugs: A Paradigm Shift-A Narrative Review

André Mansinho  1   2 , Ricardo Miguel Fernandes  3 , António Vaz Carneiro  4   5
Affiliations
Review

Histology-Agnostic Drugs: A Paradigm Shift-A Narrative Review

André Mansinho et al. Adv Ther. 2023 Apr.

Abstract

Cancer diagnosis and therapeutics have been traditionally based on pathologic classification at the organ of origin. The availability of an unprecedented amount of clinical and biologic data provides a unique window of opportunity for the development of new drugs. What was once treated as a homogeneous disease with a one-size-fits-all approach was shown to be a rather heterogeneous condition, with multiple targetable mutations that can vary during the course of the disease. Clinical trial designs have had to adapt to the exponential growth of targetable mechanisms and new agents, with ensuing challenges that are closer to those experienced with rare diseases and orphan medicines. To face these problems, precision/enrichment and other novel trial designs have been developed, and the concept of histology-agnostic targeted therapeutic agents has emerged. Patients are selected for a specific agent based on specific genomic or molecular alterations, with the same compound used to potentially treat a multiplicity of cancers, granted that the actionable driver alteration is present. There are currently approved drugs for such indications, but this approach has raised issues on multiple levels. This review aims to address the challenges of this new concept and provide insights into possible solutions and frameworks on how to tackle them.

Keywords: Early drug development; Enrichment design; New trial design; Precision medicine; Tissue-agnostic drug.

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Figures

Fig. 1
Fig. 1
Challenges in designing, conducting, and analyzing HA trials
See this image and copyright information in PMC

References

    1. Meldrum C, Doyle MA, Tothill RW. Next-generation sequencing for cancer diagnostics: a practical perspective. Clin Biochem Rev. 2011;32(4):177–195. - PMC - PubMed
    1. Mayr LM, Fuerst P. The future of high-throughput screening. J Biomol Screen. 2008;13(6):443–448. doi: 10.1177/1087057108319644. - DOI - PubMed
    1. Mario Geysen H, Schoenen F, Wagner D, Wagner R. Combinatorial compound libraries for drug discovery: an ongoing challenge. Nat Rev Drug Discov. 2003;2(3):222–230. doi: 10.1038/nrd1035. - DOI - PubMed
    1. Cui W, Aouidate A, Wang S, et al. Discovering Anti-cancer drugs via computational methods. Front Pharmacol. 2020 doi: 10.3389/fphar.2020.00733. - DOI - PMC - PubMed
    1. Tsimberidou AM, Fountzilas E, Nikanjam M, Kurzrock R. Review of precision cancer medicine: evolution of the treatment paradigm. Cancer Treat Rev. 2020;86:102019. doi: 10.1016/j.ctrv.2020.102019. - DOI - PMC - PubMed

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