Treating Colorectal Cancer with Immunotherapy: Implications for Single Versus Combination Therapy
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BASIC SCIENCE FOUNDATIONS IN COLORECTAL CANCER (S UMAR, SECTION EDITOR)
Treating Colorectal Cancer with Immunotherapy: Implications for Single Versus Combination Therapy Sophiya Karki 1 & Shahid Umar 2 & Anup Kasi 3 Published online: 20 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the USA, with most metastatic cases subsequently turning refractory to standard chemotherapy. One of the promising current interventions is immunotherapy that relies on harnessing the body’s immune mechanisms to kill the cancer cells. The aim of this review is to highlight the implications of single versus combination immunotherapy and identify the molecular features and mutations that enhance or deter responsiveness. Recent Findings Based on current findings, responsiveness is associated with deficiency of mismatch repair (dMMR) genes or presence of microsatellite instability (MSI-high), with high immunoscore and tumor mutational burden contributing to better efficacy while BRAF mutation conferring no significant effect. Combination immunotherapy demonstrates better efficacy in treating MSI-high CRC compared with single-agent immunotherapy or chemotherapy. Summary Given improved responsiveness and overall survival, there is a potential for immunotherapy to change the standard of care for metastatic CRC. Furthermore, stratifying the patients by their molecular features and mutation status is critical for establishing care. Keywords Colorectal Cancer . Immunotherapy . Microsatellite instability . Mismatch repair . Nivolumab . Pembrolizumab
Introduction Colorectal cancer (CRC) is one of the leading causes of cancer-associated deaths worldwide and the second major cause of cancer-associated deaths in the USA [1]. It is commonly known as a “silent killer” as the symptoms often do not appear until a late stage. Approximately 20–30% of CRC patients are diagnosed at an advanced stage, with those diagnosed earlier showing a high incidence of disease relapse. This article is part of the Topical Collection on Basic Science Foundations in Colorectal Cancer * Anup Kasi [email protected] 1
Department of Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
2
Department of Medicine, Division of Surgery, Kansas University Medical Center, Kansas City, KS, USA
3
Department of Medicine, Division of Medical Oncology, Kansas University Medical Center, 2650 Shawnee Mission Pkwy, Westwood, KS 66205, USA
Treatment modalities are based on tumor-nodes-metastasis (TNM) staging system provided by the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC), which relies on tumor characteristic, including the extent of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of metastases (M) [2]. However, the reliability of the TNM system in predicting CRC prognosis is debatable. This discrepancy has led to a substantial under- and overtreatment
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