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Molecular tumour boards — current and future considerations for precision oncology

Nature Reviews Clinical Oncology volume 20, pages 843–863 (2023)Cite this article

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Abstract

Over the past 15 years, rapid progress has been made in developmental therapeutics, especially regarding the use of matched targeted therapies against specific oncogenic molecular alterations across cancer types. Molecular tumour boards (MTBs) are panels of expert physicians, scientists, health-care providers and patient advocates who review and interpret molecular-profiling results for individual patients with cancer and match each patient to available therapies, which can include investigational drugs. Interpretation of the molecular alterations found in each patient is a complicated task that requires an understanding of their contextual functional effects and their correlations with sensitivity or resistance to specific treatments. The criteria for determining the actionability of molecular alterations and selecting matched treatments are constantly evolving. Therefore, MTBs have an increasingly necessary role in optimizing the allocation of biomarker-directed therapies and the implementation of precision oncology. Ultimately, increased MTB availability, accessibility and performance are likely to improve patient care. The challenges faced by MTBs are increasing, owing to the plethora of identifiable molecular alterations and immune markers in tumours of individual patients and their evolving clinical significance as more and more data on patient outcomes and results from clinical trials become available. Beyond next-generation sequencing, broader biomarker analyses can provide useful information. However, greater funding, resources and expertise are needed to ensure the sustainability of MTBs and expand their outreach to underserved populations. Harmonization between practice and policy will be required to optimally implement precision oncology. Herein, we discuss the evolving role of MTBs and current and future considerations for their use in precision oncology.

Key points

  • In the era of precision oncology, molecular tumour boards (MTBs) have an increasingly important role in optimizing treatment selection to improve outcomes by reviewing and interpreting molecular-profiling data and matching patients with appropriate available molecularly targeted therapies, which can include investigational drugs.

  • Indeed, MTB review of the interpretation of molecular alterations is crucially important for identifying matched treatment options that target the activity of the altered genes directly or within their respective established actionable genomic pathways.

  • Frequently updated criteria for the actionability of molecular alterations are essential to select and prioritize treatments, taking into consideration the level of evidence, although treatment outcomes depend on access to matched therapies and/or clinical trials.

  • Certain precision oncology trials include MTB review in routine practice; however, despite the reported clinical benefits of matched therapy, few patients can access the relevant therapies in a timely manner.

  • Standardization of and consensus regarding MTB implementation and quality requirements, novel digital platforms for data interpretation and annotation, expanded access to medications and evidence of therapeutic actionability from real-world data repositories and prospective biomarker validation studies would provide increased potential to improve patient outcomes.

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Fig. 1: Workflow of molecular tumour boards.
Fig. 2: Examples of common data elements shared between different level-of-evidence scales for the therapeutic actionability of molecular alterations.

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Acknowledgements

The work of the authors is supported in part by funds given generously to the Sheikh Khalifa al Nahyan Ben Zayed Institute of Personalized Cancer Therapy (to The University of Texas MD Anderson Cancer Center) and by The Bosarge Family Foundation (to M.K., A.J. and F.M.-B). The work of the authors is also supported in part by the NIH National Center for Advancing Translational Sciences grants UL1 TR000371 and 1U01 CA180964 (to F.M.-B.) and the NIH National Cancer Institute award number P30 CA016672 (to The University of Texas MD Anderson Cancer Center). A.M.T. acknowledges funding support from the Mr and Mrs Steven McKenzie’s Endowment and donor funds from Jamie’s Hope and Mrs and Mr Z.W. Arrott for The University of Texas MD Anderson Cancer Center Personalized Medicine Program (Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT)).

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Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Apostolia M. Tsimberidou, Henry Hiep Vo, Mehmet A. Baysal & Funda Meric-Bernstam

  2. Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Michael Kahle & Amber Johnson

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  1. Apostolia M. Tsimberidou
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A.M.T. and F.M.-B. contributed substantially to discussion of the content. All authors researched data for the article, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Apostolia M. Tsimberidou or Funda Meric-Bernstam.

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The University of Texas MD Anderson Cancer Center receives licensing fees for their Precision Oncology Decision Support (PODS) database from Philips Healthcare, which supports continued development of the PODS system. A.M.T. declares receipt of clinical trial research funding (to The University of Texas MD Anderson Cancer Center) from Agenus, IMMATICS, Novocure, OBI Pharma, Parker Institute for Cancer Immunotherapy, Tachyon, Tempus and Tvardi; fees for consulting or advisory roles for Avstera Therapeutics, Bioeclipse, BrYet, Diaccurate, Macrogenics, NEX-I and VinceRx; and travel expenses from ASCO, Cancer Care Crossroads, GenomeWeb Conference and Precision Medicine World Conference. F.M.-B. declares research funding (to The University of Texas MD Anderson Cancer Center) from Aileron Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Calithera Biosciences, Curis, CytomX Therapeutics, Daiichi Sankyo, Debiopharm, eFFECTOR Therapeutics, Genentech, Guardant Health, Klus Pharma, Novartis, Puma Biotechnology, Taiho Pharmaceutical and Takeda Pharmaceuticals; consulting or advisory roles for AbbVie, Aduro BioTech, Alkermes, AstraZeneca, Daiichi Sankyo, DebioPharm, Ecor1 Capital, eFFECTOR Therapeutics, F. Hoffman-La Roche, Genentech, GT Apeiron Therapeutics, Harbinger Health, IBM Watson, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, Lengo Therapeutics, Menarini, OrigiMed, PACT Pharma, Parexel, Pfizer, Protai Bio, Samsung Bioepis, Seattle Genetics, Tallac Therapeutics, Tyra Biosciences, Xencor and Zymeworks; honoraria from Chugai Biopharmaceuticals; and other relationships with the European Organization for Research and Treatment of Cancer and European Society for Medical Oncology. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks C. Westphalen, who co-reviewed with V. Probst; J. Sicklick and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

BRCA Exchange: https://brcaexchange.org/

CKB: https://ckb.jax.org/

ClinicalTrials.gov: https://clinicaltrials.gov/

ClinVar: https://www.ncbi.nlm.nih.gov/clinvar/

Digital ECMT cancer trial matching tool: https://trialmatch.digitalecmt.com/

gnomAD: https://gnomad.broadinstitute.org/

MASTERMIND: https://mastermind.genomenon.com/

MatchMiner: https://matchminer.org/

Model List of Essential Medicines: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02

Molecular Oncology Almanac: https://moalmanac.org/

MTBP: https://www.mtbp.org/

MTB-Report: https://bioinformatics.umg.eu/research/projects/mtb-report/

OncoKB: https://www.oncokb.org/

OncoPDSS: https://oncopdss.capitalbiobigdata.com/

OncoPubMiner: https://oncopubminer.chosenmedinfo.com/lrSearch

OpenCRAVAT: https://opencravat.org/

Personalized Cancer Therapy Knowledge Base for Precision Oncology: https://pct.mdanderson.org/

PRISM: https://prism.center/

The TP53 Database: https://tp53.isb-cgc.org/

TOPOGRAPH: https://topograph.info/home.php

TuPro: https://eth-nexus.github.io/tu-pro_website/project/

Uniprot: https://www.uniprot.org/

WAYFIND-R: https://www.wayfind-r.com/

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Tsimberidou, A.M., Kahle, M., Vo, H.H. et al. Molecular tumour boards — current and future considerations for precision oncology. Nat Rev Clin Oncol 20, 843–863 (2023). https://doi.org/10.1038/s41571-023-00824-4

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