Paulina Chmiel

Opinion Statement The current landscape of second-line treatment for cholangiocarcinoma (CCA) appears to be evolving, with emerging strategies offering potential improvements over traditional approaches. Although conventional chemotherapy demonstrates limited efficacy following progression after first-line therapy, the development of targeted therapies and immunotherapies is creating new possibilities for enhancing clinical outcomes. The increasing focus on molecular biomarkers—such as isocitrate dehydrogenase (IDH), B-raf kinase (BRAF), and neurotrophic receptor tyrosine kinase (NTRK) mutations, as well as fibroblast growth factor receptor (FGFR2) fusions and HER2/neu overexpression—represents a significant advancement in enabling precise, targeted treatment options. Evidence from recently completed and ongoing clinical trials evaluating these therapies, both as monotherapy and in combination with chemotherapy and/or immunotherapy, supports this shift. Continued research aimed at refining treatment selection and advancing personalized therapeutic strategies is essential, with the goal of achieving longer survival and improved quality of life for patients undergoing second-line therapy for CCA.

Hepatocellular carcinoma (HCC) is a malignancy with a complex pathogenesis, course, and prognosis with increasing incidence. The most significant contributing factor to the development of HCC is the chronic process of inflammation and remodeling of the cirrhotic liver, in which the interaction between the tumor microenvironment (TME) and cancer cells plays a pivotal role. In recent years, increasing focus has been directed toward the role of platelets (PLTs) in mediating interactions between tumor cells and the TME and in the progression and spread of HCC, as well as other cancers. Due to their abundance in the bloodstream and intracellular granules rich in mediators facilitating their ability to modulate the immune system, PLTs play a significant role in carcinogenesis. In the context of HCC, the role of PLTs in the healing and regeneration processes of the liver has been recognized for some time. In recent years, there has been an increasing utilization of PLTs in prognostic models for patients with HCC. Given their role and the availability of clinical options that block PLTs’ action, clinical trials of platelet blockers in the adjunctive treatment of HCC are becoming increasingly common. However, further research, both preclinical and clinical, is necessary to fully elucidate the role of PLTs in HCC and their potential use as a therapeutic target. In this literature review, we summarize the current knowledge on PLTs in HCC and focus on their potential use in everyday clinical practice.