Cancer discovery
-
TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex steroids could contribute to the male predominance of severe infections, and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.
-
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. ⋯ Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943-62. ©2017 AACR.
-
Personalized oncology aims to tailor therapy by targeting the unique genetic characteristics of a patient's tumor, whereas cancer immunotherapy focuses on activating the patient's immune system to control the tumor. The fusion of these ostensibly separate strategies has created a new dimension for personalized cancer immunotherapy. This entails the development of next-generation cancer vaccines that target neoantigens as well as the use of mutational signatures as predictive biomarkers for clinical response. The optimal use of immunotherapeutic agents will hinge on a robust understanding of the mutational profile of a cancer's genome that significantly dictates antitumor immunity and immunotherapeutic response. ⋯ Cancer immunotherapy has provided substantial clinical benefit in a significant number of patients with advanced disease. However, the need for more precise immunotherapies and predictive biomarkers remains pressing. Recent progress in these areas has been promising and has created a framework for precision immune-oncology. Cancer Discov; 6(7); 703-13. ©2016 AACR.
-
There have been significant advances in the past several years with regard to targeted therapy and immunotherapy for cancer. This is highlighted in melanoma, where treatment with targeted therapy (against the BRAF oncoprotein) results in responses in the majority of patients, although the duration of response is limited. In contrast, treatment with immunotherapy results in a lower response rate, but one that tends to be more durable. Insights about mechanisms of response and potential synergy between these treatment strategies for melanoma are a focus of this review, with opportunities to extend these insights to the treatment of other cancers. ⋯ Two major advances in melanoma have occurred concurrently and involve treatment with targeted therapy and immune checkpoint blockade. However, each of these approaches has limitations with regard to overall response rates or duration of response. To address this, investigators have proposed combining these strategies, and this concept is being tested empirically in clinical trials. There is a scientific rationale supporting the combination of targeted therapy and immunotherapy, and these concepts are discussed herein.