Review of precision cancer medicine: Evolution of the treatment paradigm

• Published in: Cancer treatment reviews Vol. 86; p. 102019
• Main Authors: Tsimberidou, Apostolia M., Fountzilas, Elena, Nikanjam, Mina, Kurzrock, Razelle
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2020
• Subjects: Biomarkers, Tumor - metabolism; ctDNA; Genomic landscape; Genomics - methods; Humans; Matched therapy; Molecular profile; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - therapy; Personalized; Precision; Precision Medicine - methods; Randomized Controlled Trials as Topic; Molecular profile; Matched therapy; Personalized; Precision; Genomic landscape; ctDNA
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2020.102019

•Genomic studies have revealed that tumors are significantly heterogeneous and complex and therefore optimized therapy does not often result from classical clinical research and practice models.•Complete tumor and cell-free DNA profiling, exome sequencing, transcriptomics, proteomics, and exploration of the immune machinery hold the promise of complete characterization of drivers of carcinogenesis.•Precision oncology focuses on gene-directed, histology-agnostic treatments, which are individualized for each patient on the basis of biomarker analysis, and immunotherapy, including adoptive cell therapy.•Innovative trial designs, including “N of 1” models, will enable optimization of treatment for individual patients and to expedite drug discovery and approval. In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology.