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Review
. 2021 Apr;6(2):100040.
doi: 10.1016/j.esmoop.2020.100040. Epub 2021 Feb 2.

Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards

R Danesi  1 , S Fogli  1 , S Indraccolo  2 , M Del Re  1 , A P Dei Tos  3 , L Leoncini  4 , L Antonuzzo  5 , L Bonanno  6 , V Guarneri  7 , A Pierini  8 , G Amunni  9 , P Conte  7
Affiliations
Review

Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards

R Danesi et al. ESMO Open. 2021 Apr.

Abstract

The therapeutic landscape of cancer is changing rapidly due to the growing number of approved drugs capable of targeting specific genetic alterations. This aspect, together with the development of noninvasive methods for the assessment of somatic mutations in the peripheral blood of patients, generated a growing interest toward a new tumor-agnostic classification system based on 'predictive' biomarkers. The current review article discusses this emerging alternative approach to the classification of cancer and its implications for the selection of treatments. It is suggested that different types of cancers sharing the same molecular profiles could benefit from the same targeted drugs. Although recent clinical trials have demonstrated that this approach cannot be generalized, there are also specific examples that demonstrate the clinical utility of this alternative vision. In this rapidly evolving scenario, a multidisciplinary approach managed by institutional Molecular Tumor Boards is fundamental to interpret the biological and clinical relevance of genetic alterations and the complexity of their relationship with treatment response.

Keywords: Molecular Tumor Board; biomarker; cancer; oncogenic drivers; target therapy.

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Conflict of interest statement

Disclosure RD serves on the scientific advisory board and has consulting relationship with Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, EUSA Pharma; and reports support for travel, accommodation, and expenses from Ipsen, and Sanofi Genzyme. SF serves on the scientific advisory board of, has consulting relationship with, and reports receiving support for travel expenses from Novartis, Teva, Roche, BMS, Lilly. MDR serves on the scientific advisory board and has consulting relationship with Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Pierre-Fabre, Janssen; and reports support for travel, accommodation, expenses from Ipsen, AstraZeneca, Sanofi Genzyme. APDT serves on the advisory boards of Roche, Bayer, Novartis, and reports receiving a travel grant from PharmaMar. VG serves on the advisory board and speakers' bureau of Lilly and Novartis (Advisory board and speakers' bureau), and reports receiving an institutional research grant from Roche. AP is an employee of Roche and has integrated access to data. SI, LL, LA, LB, GA, and PC have nothing to disclose.

Figures

Figure 1
Figure 1
The process of target validation including biomarker development.
Figure 2
Figure 2
Composition and function of the Molecular Tumor Board (MTB).
Figure 3
Figure 3
Work flow—from patient enrollment to pharmacological treatment selection.
See this image and copyright information in PMC

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