HSPG2 deposition creates a permissive environment for invasion and metastasis, and depletion of HSPG2 not only impairs metastasis but also improves chemotherapy efficacy in pancreatic tumors harboring a GOF p53 mutation71, providing a potential avenue toward targeting the stromal feedback of aggressive subsets rather than manipulation of the CAF phenotype. This evidence concerns the gene TP53 and pancreatic neoplasm.