Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide and the second leading cause of cancer-related mortality. Currently, only about 15% of newly diagnosed CRC cases and 5% of metastatic cases are classified as being microsatellite instability-high (MSI-H) and can benefit significantly from immune checkpoint blockade, while the majority of patients are microsatellite stable (MSS) and typically show limited responses to this strategy. This review aims to describe recent advances and emerging perspectives regarding the use of novel checkpoint inhibitors for MSS CRC. We conducted a structured review and critical analysis of the most relevant evidence on immunotherapy in CRC. Particular focus was placed on response outcomes in MSS CRC populations treated with enhanced anti-CTLA-4 antibody botensilimab (BOT) and the anti-PD-1 antibody balstilimab (BAL). The combination of BOT+BAL has shown promising efficacy in heavily pretreated or refractory CRC, with objective response rates up to 20% and disease control rates around 60%. In the neoadjuvant setting, the BOT+BAL regimen has produced unprecedented pathologic complete response (pCR) rates for MSS CRC tumors, achieving a pCR rate of up to 40% and partial responses up to 71%. Treatment was associated with manageable toxicity and no surgical delays, resulting in downstaging levels that may spare surgery and/or adjuvant chemotherapy. Current evidence suggests a potential shift in the therapeutic landscape of CRC. Immunotherapy benefits may extend beyond MSI-H tumors, offering new possibilities for the broader population of patients with MSS CRC.
Thaís Sampaio Corrêa de Almeida, M. I. Braghiroli, J. Sabbaga et al.· American Journal of Clinical...· 0 citations
Cholangiocarcinoma (CCA), the second most common hepatic malignancy after hepatocellular carcinoma, presents a significant clinical challenge. This epithelial cell malignancy occurs in various anatomical subtypes, including intrahepatic, perihilar, and distal, each associated with unique genetic aberrations, clinical presentations, and treatment options. Early diagnosis is challenging, leading to poor survival rates, especially in advanced cases. Precision medicine offers hope for improved management of CCA by tailoring treatments based on molecular profiling. In recent years, the investigation of eight specific molecular aberrations has emerged as a promising avenue for targeted therapy in CCA. These include six oncogenic gene alterations (HER2 overexpression, IDH1 mutations, FGFR2 fusions, BRAF mutations, NTRK fusions, and RET fusions) as well as two immunotherapy-predictive biomarkers (TMB-H [tumor mutational burden-high] and MSI-H/dMMR [microsatellite instability-high/mismatch repair deficiency]). Studies have revealed distinct therapeutic approaches for each aberration, such as HER2-targeted therapies, IDH1 inhibitors, selective FGFR inhibitors, immune checkpoint inhibitors for TMB-H and MSI-H/dMMR cases, and RET kinase inhibitors. Notably, some of these treatments have received FDA approval, providing new hope for patients with these specific molecular profiles. The era of precision medicine shows promise in revolutionizing the diagnosis and treatment of CCA, improving patient outcomes and prognosis. The aim of this review is to summarize recent advances in precision medicine for cholangiocarcinoma (CCA), focusing on the identification of specific molecular aberrations and their corresponding targeted therapeutic interventions.
Augusto Almeida, Joao Manzi, Camila Hoff et al.· Translational Oncology· 0 citations
