Abstract
Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact of Cav-1 expression in a cohort of 39 metastatic PDAC patients treated with different first-line chemotherapy regimens. We also assessed the predictive value of Cav-1 in patients treated with gemcitabine and nab-paclitaxel. Cav-1 expression was evaluated by immunohistochemistry staining in neoplastic and stromal cells, using metastatic sites or primary tumor tissue specimens. Higher levels of Cav-1 expression were associated with significantly worse overall survival (OS) and progression-free survival (PFS). No differences in OS were found between patients treated with gemcitabine + nab-paclitaxel vs. other chemotherapy options. Multivariate analysis for OS and PFS confirmed the independent prognostic role of Cav-1 expression. Our study evidenced a negative prognostic role of Cav-1 in patients affected by metastatic/locally advanced unresectable PDAC. Moreover, Cav-1 expression seems not to predict different response rates to different types of first-line treatment. Future prospective trials will be necessary to confirm the prognostic role of Cav-1 and explore Cav-1 specific inhibitors as a therapeutic option for advanced PDAC patients.
Highlights
Despite improvements in surgical and medical treatments, pancreatic ductal adenocarcinoma (PDAC) still represents one of the deadliest malignancies
Late diagnosis and rapid progression of the disease together with resistance to chemotherapy and radiotherapy contribute to PDAC dismal prognosis
PDAC is characterized by a dense fibrotic stroma, which represents a physical barrier for therapies and has an established role in promoting cancer progression
Summary
Despite improvements in surgical and medical treatments, pancreatic ductal adenocarcinoma (PDAC) still represents one of the deadliest malignancies. Gemcitabine has been the mainstay of treatment of both resected and metastatic PDAC for many years while more recently, the combination regimens of either 5-fluorouracil (5-FU)/leucovorin with irinotecan and oxaliplatin (scheme FOLFIRINOX), or gemcitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) have become the standard of care in different settings on the basis of phase III clinical trials showing superior outcomes with either of the combinations over gemcitabine alone [2,3,4] This scenario highlights the need for identification of biomarkers associated with disease prognosis with utility to select patients for different treatments
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