Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged.
Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase.
Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options.
Keywords: AKT inhibitors; KRas; MAPK kinase inhibitors; MRK-003; MS-275; PEGylated hyaluronidase; PF-03084014; Ras; Sonic hedgehog; apricoxib; c-Met; cabozantinib; celecoxib; crizotinib; cyclooxygenase-2; cytidine deaminase; delta-like ligand 4; demcizumab; desmoplasia; gemcitabine; histone deacetylases; hyaluronan; local drug eluter; notch signaling; pancreatic adenocarcinoma; urokinase; urokinase plasminogen activator receptor; vorinostat; γ-secretase inhibitors.