The translational challenges in the field of precision oncology are in part related to the biological complexity and diversity of this disease. Technological advances in genomics have facilitated large sequencing efforts and discoveries that have further supported this notion. In this review, we reflect on the impact of these discoveries on our understanding of several concepts: cancer initiation, cancer prevention, early detection, adjuvant therapy and minimal residual disease monitoring, cancer drug resistance, and cancer evolution in metastasis. We discuss key areas of focus for improving cancer outcomes, from biological insights to clinical application, and suggest where the development of these technologies will lead us. Finally, we discuss practical challenges to the wider adoption of molecular profiling in the clinic and the need for robust translational infrastructure.

Comment in Cancer Cell. 2022 May 9;40(5):447-449.

Comment in Cancer Cell. 2022 May 9;40(5):452-454. Immunity. 2022 Jun 14;55(6):979-981.

Comment in Cancer Cell. 2022 May 9;40(5):450-451.

Comment in Cell Rep Med. 2022 Jun 21;3(6):100669.

Comment in Cell Rep Med. 2022 May 17;3(5):100639.

Comment on Cancer Cell. 2022 May 9;40(5):479-493.e6.

Comment in Signal Transduct Target Ther. 2022 Jul 11;7(1):228.

Immune checkpoint inhibitors (ICIs) have limited activity in patients with castration-resistant prostate cancer (CRPC). A Nature article demonstrates that androgen receptor (AR) negatively modulates CD8+ T cell-driven antitumor immune response and that androgen-axis blockade is a promising therapeutic strategy to improve ICI activity in CRPC.

Comment on Cancer Cell. 2022 May 9;40(5):509-523.e6.

Author information: (1)Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (2)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (3)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (4)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5)Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA. (6)Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (7)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (8)Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, NY, USA. (9)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: viviana.simon@mssm.edu. (10)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: samir.parekh@mssm.edu.

Comment on Cancer Cell. 2022 May 9;40(5):545-557.e13.