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. 2023 Mar 25;15(7):1967.
doi: 10.3390/cancers15071967.

Precision Oncology: Evolving Clinical Trials across Tumor Types

I-Wen Song  1 , Henry Hiep Vo  1 , Ying-Shiuan Chen  1 , Mehmet A Baysal  1 , Michael Kahle  2 , Amber Johnson  2 , Apostolia M Tsimberidou  1
Affiliations

Precision Oncology: Evolving Clinical Trials across Tumor Types

I-Wen Song et al. Cancers (Basel). .

Abstract

Advances in molecular technologies and targeted therapeutics have accelerated the implementation of precision oncology, resulting in improved clinical outcomes in selected patients. The use of next-generation sequencing and assessments of immune and other biomarkers helps optimize patient treatment selection. In this review, selected precision oncology trials including the IMPACT, SHIVA, IMPACT2, NCI-MPACT, TAPUR, DRUP, and NCI-MATCH studies are summarized, and their challenges and opportunities are discussed. Brief summaries of the new ComboMATCH, MyeloMATCH, and iMATCH studies, which follow the example of NCI-MATCH, are also included. Despite the progress made, precision oncology is inaccessible to many patients with cancer. Some patients' tumors may not respond to these treatments, owing to the complexity of carcinogenesis, the use of ineffective therapies, or unknown mechanisms of tumor resistance to treatment. The implementation of artificial intelligence, machine learning, and bioinformatic analyses of complex multi-omic data may improve the accuracy of tumor characterization, and if used strategically with caution, may accelerate the implementation of precision medicine. Clinical trials in precision oncology continue to evolve, improving outcomes and expediting the identification of curative strategies for patients with cancer. Despite the existing challenges, significant progress has been made in the past twenty years, demonstrating the benefit of precision oncology in many patients with advanced cancer.

Keywords: IMPACT; NCI-MATCH; TAPUR; clinical trials; immunotherapy; investigational therapy; precision oncology; targeted therapy.

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Conflict of interest statement

Apostolia M. Tsimberidou: clinical trial research funding (institutions): OBI Pharma, Agenus, Parker Institute for Cancer Immunotherapy, Tempus, IMMATICS, Tvardi, Novocure, Tachyon; consulting or advisory roles: VinceRx, Diaccurate, NEX-I, BrYet, Bioeclipse, Macrogenics, Avstera Therapeutics. The remaining authors report no conflict.

Figures

Figure 1
Figure 1
Overview of molecular profiling in precision oncology. In the screening phase of a biomarker-driven trial, patients (1) undergo a tumor biopsy or blood draw (liquid biopsy) (2) that is used for tumor molecular profiling (3) to determine the drivers of carcinogenesis (genomic or protein level), if any (4). The molecular profile report is often discussed at a molecular tumor board (5) for the interpretation of tumor alterations and for matching with a targeted therapy or clinical trial (6). The patient is then treated with the assigned therapy (FDA-approved or investigational drug after screening for clinical trial) and monitored for anti-tumor effects and toxicity (7). If the disease progresses, the next treatment can again be selected from a new round of tumor or blood analyses to identify evolving biomarkers.
Figure 2
Figure 2
A timeline of clinical trials in precision oncology.
See this image and copyright information in PMC

References

    1. Druker B.J., Talpaz M., Resta D.J., Peng B., Buchdunger E., Ford J.M., Lydon N.B., Kantarjian H., Capdeville R., Ohno-Jones S., et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 2001;344:1031–1037. doi: 10.1056/NEJM200104053441401. - DOI - PubMed
    1. Rizvi N.A., Hellmann M.D., Snyder A., Kvistborg P., Makarov V., Havel J.J., Lee W., Yuan J., Wong P., Ho T.S., et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128. doi: 10.1126/science.aaa1348. - DOI - PMC - PubMed
    1. Goodman A.M., Kato S., Bazhenova L., Patel S.P., Frampton G.M., Miller V., Stephens P.J., Daniels G.A., Kurzrock R. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol. Cancer Ther. 2017;16:2598–2608. doi: 10.1158/1535-7163.MCT-17-0386. - DOI - PMC - PubMed
    1. Hellmann M.D., Callahan M.K., Awad M.M., Calvo E., Ascierto P.A., Atmaca A., Rizvi N.A., Hirsch F.R., Selvaggi G., Szustakowski J.D., et al. Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer. Cancer Cell. 2018;33:853–861.e854. doi: 10.1016/j.ccell.2018.04.001. - DOI - PMC - PubMed
    1. Rosenberg S.A., Restifo N.P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348:62–68. doi: 10.1126/science.aaa4967. - DOI - PMC - PubMed

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