Furthermore, PYK2’s role in critical tumor microenvironment processes, including stromal crosstalk (e.g., DDR1-PYK2 in PDAC (63), macrophage polarization (e.g., IRF5 phosphorylation 13), and cancer stemness maintenance (e.g., via nuclear YAP/TAZ 18), suggests its contribution to resistance against broader therapies, potentially including targeted agents and immunotherapies. This evidence concerns the gene PTK2B and cancer.