Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards
Romano Danesi, Stefano Fogli, Stefano Indraccolo, Marzia Del Re, Angelo Paolo Dei Tos, Lorenzo Leoncini, Lorenzo Antonuzzo, Laura Bonanno, Valentina Guarneri, Andrea Pierini, Gianni Amunni, PierFranco Conte
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.