Expression of Checkpoint Molecules in the Biology Diagrams This review will focus on three major areas of cell cycle transition control, with particular attention to the alterations found in human cancer. These areas include the G1/S transition, where most cancerโrelated defects occur, the G2/M checkpoint and its activation in response to DNA damage, and the spindle checkpoint. Immune checkpoint inhibitors (ICIs) block inhibitory pathways that tumour cells exploit to evade the immune system. They play a key role in the management of aggressive cancers, including non-small cell lung cancer, melanoma and Hodgkin's lymphoma. Despite their efficacy, ICIs can cause severe, potentially fatal, immune-related adverse events (irAEs), including multiorgan failure. Introduction. Immune system activation is an extremely effective anticancer therapy that has revolutionised oncological clinical practice over the last decade.1 The immune checkpoint inhibitors (ICIs) are a group of drugs that 'take the brakes' off the normal immune response and facilitate immunological, as opposed to traditional cytotoxic, anti-cancer effects.
Source Reference: Slovin SF "Immune checkpoint combos in metastatic castration-resistant prostate cancer: Where are we going, what are we doing, and why?" J Clin Oncol 2025; DOI: 10.1200/JCO-24-02402. Figure 1. Milestones in cancer research. (A) Historical milestones in cancer research include discoveries, Nobel Prizes, and FDA approvals.(B) Immune checkpoint blockade with anti-CTLA-4 and anti-PD1 antibodies acts via T cells.Upon binding to their ligands, checkpoint receptors expressed on T cells, including PD-1 and CTLA-4, mediate suppression of T cell-mediated tumor killing. It has been approved as first- or second-line therapy in many cancer types. Unfortunately, a majority of immune checkpoint inhibitor recipients are refractory to the therapy. The contribution of neutrophils to immune-checkpoint inhibitor treatment failures in cancer Pharmacol Ther. 2021 Jan:217:107662. doi: 10.1016/j.pharmthera.2020.107662
Cell cycle checkpoints and their inactivation in human cancer Biology Diagrams
Retrospective pattern-of-failure data in patients with non-small cell lung cancer (NSCLC) led to the initiation of two prospective randomized trials of local therapy plus systemic therapy versus local therapy alone [16, 17]. Both trials demonstrated that improved PFS could be achieved by treating established tumors present at baseline, but in Gut bacteria are to blame for the failure of immune checkpoint therapy for ovarian cancer, our Melanie Rutkowski, PhD, has discovered. Her findings could let us turn the failed treatment into a much-needed lifesaver. The problem, she found, comes from an unexpected source: the flagella that bacteria use to move.
