Although the overall five-year survival of patients with pancreatic cancer is dismal, there are substantial differences in disease progression, therapeutic response, and overall survival between cases with clinically and pathologically indistinguishable characteristics. Our inability to distinguish between these cases presents a major challenge in patient clinical management and continues to prevent our ability to treat this disease. Therefore, there is an urgent clinical need to better understand the molecular mechanisms behind of this disease to enable the improvement of therapeutic strategies.
Keratin 17 (K17) is a novel, tumor-cell specific biomarker that identifies the patient subgroup with the most aggressive disease in several types of solid tumor malignancies including PDAC even among patients with advanced-stage disease and in cases with negative surgical margins in PDAC. More recently, analyses of a PDAC clinical trial shows that K17-expressing PDACs are the least responsive to adjuvant therapy, suggesting that K17 can predict response to therapy. PDAC tumors are composed of immunosuppressive cells and tumor-associated stroma that contribute to poor response to chemo and immunotherapy. We and others have shown that K17 expression is associated with immune-mediated functions in tissues, and we recently observed differences in spatial relationships between tumor cells and macrophage infiltration in PDAC.
Our research focuses on understanding how K17 impacts immune cell function while enhancing tumor growth and metastasis. Additionally, we aim to determine the biological contribution of K17 on tumor aggression and response to standard-of-care therapeutic agents. These studies may lead to the development of a novel prevision medicine tool and can provide pre-clinical evidence of a novel therapeutic target in PDAC.
Pancreatic Ductal Adenocarcinoma