There is renewed interest in MSI analysis because the MSI-H/dMMR phenotype has emerged as an actionable predictive biomarker for immune checkpoint blockade therapy in different cancer types. This review presents available evidence supporting the clinical relevance and predictive value of MSI/dMMR in cancers, including those treated with immune checkpoint inhibitors (ICIs), and outlines the diagnostic approaches developed to assess MSI/dMMR in clinical practice.
PD-L1 expression is a rational biomarker to predict response to PD-1/PD-L1 ICI therapy, and has been studied extensively in clinical trials. A recurring theme emerging from available clinical data is that high levels of tumor cell membrane PD-L1 expression correlate with better outcomes with PD-1/PD-L1 blockade.
Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer death among women in the United States.1 No effective screening tests are available, and more than 70% of patients are diagnosed with advanced-stage disease.2
More recently, immunologic therapy has emerged as an important treatment option for many types of cancers, based on demonstrations of unprecedented efficacy. This radical shift in treatment has come with the recognition of the essential role of the immune system in the surveillance and eradication of neoplastic cells, particularly modulation of the immune checkpoint protein cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and the programmed death-1 (PD-1) receptor and its ligand, PD-L1.
The fluoropyrimidine 5-fluorouracil (5-FU) and its prodrug capecitabine are cytotoxic agents that have been widely used in the treatment of solid tumors. In the United States alone, an estimated 275,000 patients with cancer receive 5-FU each year. Despite its lifesaving/life-prolonging potential, 5-FU causes severe early-onset toxicity in up to one-fourth of patients, and more than 1300 die each year as a result of this toxicity.
In 1979, Falck and colleagues described the presence of chemotherapy in the urine of nurses caring for patients who had received chemotherapy.1
The discovery that merely handling chemotherapy drugs can lead to absorption of the chemotherapy drugs has been key in the re-evaluation of safety in healthcare environments. In 2004, the National Institute for Occupational Safety and Health (NIOSH) alert noted that skin rashes, infertility, miscarriage, birth defects, and leukemia or other cancers may be associated with working with or near hazardous drugs.2