Emerging antibodies for the treatment of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.

Identification of biomarkers and their functions in dasatinib‑resistant pancreatic cancer using bioinformatics analysis

“…In pancreatic cancer, vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF1R) or matrix metalloproteinases (MMPs), such as MMP-9, are commonly overexpressed, which allows treatment of pancreatic cancer using certain small molecule inhibitors against these proteins (22,23). Dasatinib is a potent receptor tyrosine kinase/Src inhibitor, which reduces pancreatic tumor cell growth in vitro (11).…”

Molecular biology in pancreatic ductal adenocarcinoma: implications for future diagnostics and therapy

“…Disappointingly, singleagent immunotherapy has had little effect in PDAC [54]. Increasing evidence suggests that the PDAC microenvironment is comprised of an intricate network of signals between immune cells, PDAC cells and stroma, resulting in an immunosuppressive environment resistant to single-agent immunotherapies [54,55]. It has also been shown that a higher density of CD3+ T-cells in the stroma is associated with longer progression-free survival in patients with PDAC [56], and that combination of mutational profiles and immune markers may define subgroups of patients who may respond to specific types of therapies [57].…”

Second-line therapy in advanced upper gastrointestinal cancers: current status and new prospects

“…By inhibiting inflammationpromoted cancer progression, the JAK-STAT inhibitor ruxolitinib achieved promising outcomes in preclinical and phase II trials ( 65), but the subsequent phase III trial was terminated prematurely after demonstration of insufficient efficacy at a planned interim analysis of the JANUS1 trial. Additional strategies involved inhibitors of EGFR, HER2, IGF-1, VEGF, NOTCH, WNT and farnesyl-transferase pathways mainly in combination with gemcitabine (66). Early trials indicate that patients carrying BRCA mutations may benefit from platinum agents and PARP inhibitors.…”