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The Next Horizon in Precision Oncology

Proteogenomics characterizes tumors molecularly, makes the diagnosis more accurate, and can potentially impact cancer treatment, improving outcomes in our patients. This perspective published by Cell in April 2021, describes the significant contributions of The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium to precision oncology. It also makes the case that proteogenomics should be integrated to clinical trials and patient care, to finally provide the right treatment at the right dose for the right patient at the right time.

There are no identical tumors from a patient to another. However, they may share similar genetic and molecular alterations susceptible to targeted treatments. This perspective also underlines the role of the National Cancer Institute (NCI) at the National Institutes of Health (NIH) and its priceless contribution with The Cancer Genome Atlas to Clinical Proteomic Tumor Analysis Consortium (CPTAC) whose results will set the foundation for the next horizon in precision oncology: protegenomics.

The advances in cancer therapy in the last 40 years are unprecedented. Precision oncology made its stage appearance in the late 90s with the demonstration of the efficacy of trastuzumab (Herceptin) for breast cancers overexpressing HER2 oncoprotein. Subsequently, imatinib (Gleevec) targeted BCR-ABL1 kinase demonstrated efficacy in patients with chronic myelogenous leukemia. These early advances fueled the research and discovery of new small molecules and antibodies for multiple types of malignancies. For instance, the analysis of gastric cancer by TCGA revealed that there are 4 molecular types of gastric cancer, one of them containing EBV genome, had PIK3CA mutation in 80%, and recurrent amplification of PDL-1 and PDL-2 locus which may suggest opportunities to evaluate the efficacy of immune checkpoint inhibitors.

Although all the advancements from proteogenomics are promising, there are still gaps that need to be filled. In that sense, collaboration is key and has already demonstrated outstanding results. The CPTAC in collaboration with the NCI's clinical trials has elucidated the genomic landscape of 13 malignancies with potential targets. We still need to figure out the clinical relevance of many of these genetic variations and their products, and the most appropriate targets for therapy.