Gastrointestinal Cancers
Early insights for CPI combinations in solid tumors
mmunotherapy using anti-PD-1 immune checkpoint inhibitors (CPIs), which is a major therapeutic option in oncology, can potentially achieve synergistic effects once combined with targeted therapies. Drugs targeting proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2), can improve therapeutic responsiveness through their immunosuppressive activity in the tumor environment.
Anti-PD-1 compounds targeting MSI-H/dMMR tumors
Accurate and timely repair of DNA is essential for maintaining genetic stability. Microsatellites are repetitive DNA sequences and particularly prone to replication errors that are normally repaired by the mismatch repair system. Mismatch repair-deficient tumors (dMMR) harbor many mutations in microsatellites, resulting in high levels of microsatellite instability (MSI-H).
Checkpoint inhibition: predictors, resistance and immunogenomic features
Immune checkpoints, such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) or programmed cell death protein 1 (PD-1), downregulate T-cell responses and are crucial for self-tolerance, which protects the body against attacking cells indiscriminately. Tumor cells hijack this mechanism to evade the immune system through the activation of immune checkpoints and inhibition of the T-cell response.
Novel approaches in gastric cancer
With more than 1 million newly diagnosed cases in 2020, gastric cancer was at the fifth place (5.6 %) of the most frequent malignant diseases and accounted for nearly 8 % of cancer deaths worldwide. The multicohort, non-randomized, open-label, phase II LEAP-005 study (NCT03797326) was designed to evaluate the safety and efficacy of a combination – the anti-angiogenic multikinase inhibitor lenvatinib plus the anti-PD-1 antibody pembrolizumab – in patients with previously treated advanced solid tumors.