168 CHAPTER 6 Furthermore, with the rise of multi-omics analyses on clinical cancer tissue samples, there is a high need for computational models to help integrating –omics data from multiple layers of biology68. The development of an integrated bioinformatics pipeline for data analysis would help advancing precision oncology even more in the future. Knowledge on how genomic features translate to RNA, protein expression and post-translational modifications is still relatively scarce and would benefit our understanding of cancer biology. PROGRESS MADE IN PRECISION ONCOLOGY AND TARGETED THERAPY SELECTION Generation of knowledge on cancer biology, the development of molecular diagnostic techniques and the availability of new targeted drugs have fundamentally changed oncology practice worldwide. How did these advances concretely benefit the care for patients with cancer? For many individual patients with different tumor types, extensive genomic testing revealed unexpected driver mutations, resulting in an extra treatment option within a clinical trial such as DRUP. The data resulting from these experimental treatments may ultimately lead to an expansion of the labeled indications of targeted drugs. This has already been the case for nivolumab, which is now approved and reimbursed in the Netherlands for patients with MSI/ dMMR tumors, regardless of histology69. Another example is the addition of BRCA-mutated prostate cancer to the label for olaparib, a PARP inhibitor, largely based on the PROFOUND data70. Specifically for patients with rare cancers, additional molecular-guided treatment options are highly valued, since they commonly have less treatment opportunities and are understudied at the level of genomic targets19. Genomics-guided treatment selection benefits patients in more than one way. Apart from generating extra treatment options, it is also essential to withhold treatments if patients have specific molecular or clinical features that render their tumors insensitive to targeted agents. For example, based on molecular profiling, treatment with anti-EGFR monoclonal antibodies for patients with colorectal cancer with a KRAS, NRAS or BRAF mutation has been terminated due to a lack of clinical benefit 71-73. CONCLUDING REMARKS EN FUTURE PERSPECTIVES: EYES ON THE PRIZE Precision oncology has come a long way since the introduction of the first targeted drug (trastuzumab) in 1999. Broad molecular testing of tumor tissue has vastly expanded our knowledge of the biology of cancer, leading to a steep increase in the number of approved targeted drugs and an expansion of the labeled indications of these drugs. Off-label use of these new classes of targeted drugs is nowadays better documented and often performed in clinical trials to maximize the learning potential of these experimental treatments for the medical community. As long as no “cure for cancer” exists, there will be room for improvement of our knowledge and approach to treating patients with cancer.
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