Current Colorectal Cancer Reports最新文献

Purpose of review: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the United States, 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 to single agent immunotherapy or chemotherapy.

Summary: Given improved responsiveness and overall survival, there is 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.

Purpose of review: Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. Our purpose is to recapitulate historical and recent genomic research in order to augment the understanding of colorectal cancer pathogenesis.

Recent findings: In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents.

Summary: In this review, we expound on the current literature as well as draw on our own experience to present the important molecular pathogenesis pathways, key genetic mutations, differences in pathogenesis of left versus right sided tumors as well as the molecular classification of colorectal cancers.

Purpose of review: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).

Recent findings: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.

Summary: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.