Clinical application of genomics- and phosphoproteomics-based selection of targeted therapy in patients with advanced solid tumors

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.

General improvements in the logistics, availability of targeted drugs and access to diagnostics and expertise will likely have the greatest impact on direct benefit for patients. In the future, standardized processing and conservation of tumor tissue/biopsies should be possible in all healthcare facilities, and collaborations and sharing of knowledge and resources with the academic institutes will be viable to delivering precision oncology to all patients. If these conditions are met, more patients may potentially benefit from the knowledge and new treatment options resulting from the precision oncology trials. Also, medical oncologists may learn more about molecular testing and interpreting test results from participation in MTBs. To maximize the impact of precision oncology, international collaborations are of utmost importance and research groups throughout the world are encouraged to share best practices and creative solutions to overcome the hurdles that still hamper new initiatives in the field today.
Future clinical research may focus on prospective therapy selection using molecular information from other –omics fields, such as phosphoproteomics, especially in patients where no clear monogenetic driver mutations is identified and a comprehensive pathway analysis may give more direction for potential therapeutic strategies. More knowledge on the best method of prioritizing targets for treatments will be essential, as well as clinical trials investigating new combinations of targeted agents.
With an increasing understanding of cancer biology and improved strategies for treatment selection, precision oncology will be accessible for patients with advanced cancer and more patients will benefit from the knowledge that we gain today and tomorrow. In the future, treatments based on histology alone may be considered old-fashioned, and multi-omics diagnostics may result in a comprehensible report that can be easily interpreted, and will directly guide treatment decisions for individual patients.