Colon cancer is known to be resistant to immunotherapy; however, during the last few years, researchers managed to identify a subgroup of patients that response to anti-PD-1 therapy. This encouraged molecular biologists, immunologists, and clinical oncologists to reconsider the role of immunotherapy for colon cancer. A substantial number of studies devoted to this problem have been published so far, which allowed us to prepare a literature review. This review covers the main trends in immunotherapy of colon cancer, including prognostic value of tumor-infiltrating lymphocytes, efficacy of immune checkpoint inhibitors, bispecific monoclonal antibodies, and antitumor vaccines, as well as transformation of non-inflammatory cancer phenotype into the inflammatory one.
Objective: to determine the efficacy of 2 oxaliplatin-based chemotherapy regimens (FOLFOX and XELOX) for metastatic colorectal cancer (CRC) depending on the KRAS mutation status and primary tumor location. Materials and methods. We performed retrospective analysis of the data on patients with metastatic CRC taken from a prospective database. We included patients with known KRAS mutation status that received either FOLFOX or XELOX without targeted drugs. Progression-free survival (PFS) was used as a main criterion in estimating treatment efficacy. Results. The inclusion criteria were met by 157 patients. The FOLFOX regimen was more effective in patients with wild-type KRAS CRC: median PFS was 10 months versus 8 months in the XELOX group (hazard ratio (HR) = 0.7; 95 % confidence interval (CI) 0.4–1.2; р = 0.1). However, we observed no significant differences in median life expectancy between these groups: it was 37 and 38 months respectively (HR = 1.1; 95 % CI 0.6–2.1; p = 0.6). Similar trends were observed in patients bearing KRAS mutations: median PFS in the FOLFOX group was 9 months vs 5 months in the XELOX group (HR = 0.6; 95 % CI 0.3–1.2; р = 0.1; p value by Breslow – Day test = 0.04). No differences in median life expectancy between these groups were observed: 33 and 23 months respectively (HR = 0.8; 95 % CI 0.4–1.6; p = 0.5). Conclusion. We failed to find an association between the KRAS mutation status and response to a particular chemotherapy regimen. We found that patients with metastatic CRC receiving the FOLFOX regimen were more likely to achieve objective responses and demonstrated higher median PFS than patients on the XELOX regimen.
Introduction. The concordance of KRAS gene mutation status between the primary and metastatic CRC is 95%. The aim of this study was to find factors associated with the disconcordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in pts with CRC. Patients and methods. We performed DNA melting analysis with TaqMan probes and following Sanger sequencing to detect mutation hot-spots in KRAS exons 2 and 3, NRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20 in 148 tumor tissues from 65 pts (65 primary tumors and 83 metastases). Results. Mutations in KRAS, NRAS, PIK3CA and BRAF genes in primary tumors were detected in 43.1%, 3.1%, 13.8% and 3.1%, respectively. Discordance of mutation status of genes was identified in 29.2% of patients: 16.9% in KRAS, 3% in NRAS, 12.3% in PIK3CA and 3% BRAF status. In all cases of metastases in the brain we found the discordance in KRAS and PIK3CA mutation status (p=0.08). Also, peritoneal metastases had discordance in KRAS status (p=0.02). With the increase of period from removal of the primary tumor and metastases, the incidence rate of changes in the mutational status of the genes also increased. Conclusion. discordance of the mutational status of genes, especially in the long course of the disease, raises the question of repeating biopsies in the progression of the disease