Bridging Cancer and COVID-19: The Complex Interplay of ACE2 and TMPRSS2

The coronavirus disease 2019 (COVID-19) pandemic presents heightened risks for cancer patients, who are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes due to immunosuppression from both the malignancy and anticancer therapies. This review investigates the dual roles of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in SARS-CoV-2 infection among cancer patients. ACE2, the vital entry receptor for SARS-CoV-2, is overexpressed in certain tumors such as colon adenocarcinoma, renal carcinomas, pancreatic adenocarcinoma, and lung adenocarcinoma, potentially increasing viral susceptibility. Paradoxically, ACE2 also exhibits tumor-suppressive properties by inhibiting angiogenesis and modulating the tumor microenvironment, leading to improved patient prognoses in some cancers like breast cancer. TMPRSS2, essential for viral entry, shows decreased expression in several tumors but acts as a prognostic biomarker in prostate and lung cancers. This review illustrates the complexity of therapeutically targeting ACE2 and TMPRSS2 due to their contrasting roles in cancer progression and viral entry. We analyze the expression levels of ACE2 and TMPRSS2 in relation to immune cell infiltration and patient outcomes, and propose personalized therapeutic strategies. Furthermore, we underscore the necessity for multidisciplinary approaches, integrating antiviral treatments with cancer therapies and tailoring interventions based on individual molecular profiles. This approach to personalized medicine seeks to enhance treatment results and better manage cancer patients who have contracted SARS-CoV-2.