Aspirin for colorectal cancer with PIK3CA mutations: the rising of the oldest targeted therapy?

A recent report in The New England Journal of Medicine by Liao and colleagues highlights the benefit of aspirin use in a molecular defined subgroup of patients affected by metastatic colorectal cancer (CRC). Authors concluded that it is very likely that the regular use of aspirin after CRC diagnosis is associated with longer survival among patients with mutated-PIK3CA tumors. In contrast, aspirin has no effect on cancer-specific survival in patients with wild-type PIK3CA CRC (1). The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays an important role in carcinogenesis of CRC. Activating mutations in PIK3CA occur in two “hotspots” located in exon 9 (E542K, E545K) and exon 20 (H1047R) in approximately 15% of CRCs (2). PIK3CA encodes for a lipid kinase that regulates signaling pathways downstream of the Epidermal Growth Factor Receptor (EGFR), and its mutations hamper sensitivity to the anti-EGFR monoclonal antibodies cetuximab or panitumumab registered for metastatic CRC treatment (3,4).