Cancer genetic profile and risk of thrombosis

Cancer-associated thrombosis (CAT) remains a leading cause of morbidity and mortality among oncology patients, with an incidence influenced by tumor type, stage, treatment, and molecular characteristics. This review explores the molecular determinants of venous thromboembolism (VTE) in cancer, emphasizing its pathophysiology and association with specific oncogenic alterations.

Certain molecular profiles exhibit heightened VTE risk. In lung cancer, due to hypercoagulability mechanisms linked to tissue factor overexpression, an increased incidence of VTE has been reported in populations with ALK (30–40 %) and ROS1 rearrangements (34.7–46.6 %). In gastrointestinal cancers, while pancreatic adenocarcinoma has the highest VTE rates (up to 22 %), KRAS mutations seem to be implicated but not conclusively validated. Similarly, colorectal cancer mutations (KRAS/BRAF^V600E) and antiangiogenic therapies may elevate thrombotic risk, warranting further study.

High-grade gliomas, particularly glioblastomas, present VTE rates up to 30 %, driven by podoplanin-induced platelet aggregation. IDH1 mutations inversely correlate with thrombosis, highlighting its protective role. Emerging evidence suggests that agnostic biomarkers such as STK11 mutations influence VTE risk across tumor types, while others like KRAS, MET and BRCA mutations show inconclusive results. Large-scale validation studies are imperative to integrate molecular profiles into clinical practice. Until then, management decisions should be individualized, balancing the thrombotic risks with oncologic considerations.