There have been significant improvements in the survival of patients with metastatic colorectal cancer (mCRC) over the past decade. However, patients with the disease who fail to respond to first- or second-line therapies, including chemotherapy and monoclonal antibodies, have few treatment options. Advances in subsequent treatment lines rather than in first- or second-line therapies now drive improvements in survival for these patients.
Following the advent of molecularly targeted agents, and more recently, immunotherapy, over the past few decades, we have witnessed dramatic changes in the treatment paradigms for many types of cancer. These advancements were driven by molecular profiling that enabled the identification of those patient populations most likely to benefit from targeted therapy and/or immunotherapy—that is, precision medicine.
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.
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.
Lung cancer is the leading cause of death from cancer worldwide, estimated to be responsible for nearly 1 in 5 cancer deaths in 2012 (1.59 million deaths, 19.4% of total cancer deaths).1 In the United States, lung cancer is the second most frequently diagnosed cancer, with an estimated 224,390 new cases in 2016, representing the leading cause of cancer death in Americans.2,3