Immunotherapy for Colorectal Cancer in the Era of Precision Medicine

Colorectal cancer (CRC) is considered the third most common cancer type and the second cause of cancer-related death worldwide, representing a significant global public health issue. Approximately 20% of patients present with metastatic disease, while up to 50% of those with early stages will eventually develop metastasis. During the last two decades, sustained efforts have been made to discover the molecular landscape of CRC and identify novel therapeutic targets. These efforts changed the treatment paradigm for CRC and improved survival significantly in metastatic disease. Immunotherapy represents a novel and exciting treatment option with promising results in gastrointestinal malignancies. The application of immunotherapy in CRC showed impressive results in a subset of patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) phenotype. An in-depth analysis of these particular MSI-H/dMMR tumors revealed that they are characterized by a high mutational load resulting in an increased number of neoantigens and a highly infiltrated tumor microenvironment. The Food and Drug Association (FDA) has recently approved immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab +/− ipilimumab for first-line and non-first-line therapy of MSI-H/dMMR metastatic CRC, contributing to the continuum of care in these patients. This chapter aims to overview the immune landscape and immunotherapeutic strategies in CRC

Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives

Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy

Practical Considerations for the Use of Cannabis in Cancer Pain Management—What a Medical Oncologist Should Know

Pain is a highly debilitating emotional and sensory experience that significantly affects quality of life (QoL). Numerous chronic conditions, including cancer, are associated with chronic pain. In the setting of malignancy, pain can be a consequence of the tumor itself or of life-saving interventions, including surgery, chemotherapy, and radiotherapy. Despite significant pharmacological advances and awareness campaigns, pain remains undertreated in one-third of patients. To date, opioids have been the mainstay of cancer pain management. The problematic side effects and unsatisfactory pain relief of opioids have revived patients’ and physicians’ interest in finding new solutions, including cannabis and cannabinoids. The medical use of cannabis has been prohibited for decades, and it remains in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context for its usage has become more permissive. Various preclinical and observational studies have aimed to prove that cannabinoids could be effective in cancer pain management. However, their clinical utility must be further supported by high-quality clinical trials

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade

Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/− ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use