Gemcitabine-Lipid Conjugate and ONC201 Combination Therapy Effectively Treats Orthotopic Pancreatic Tumor-Bearing Mice.

Gemcitabine (GEM) is a nucleoside analogue approved as a first line of therapy for pancreatic ductal adenocarcinoma (PDAC). However, rapid metabolism by plasma cytidine deaminase leading to the short half-life, intricate intracellular metabolism, ineffective cell uptake, and swift development of chemoresistance downgrades the clinical efficacy of GEM. ONC201 is a small molecule that inhibits the Akt and ERK pathways and upregulates the TNF-related apoptosis-inducing ligand (TRAIL), which leads to the reversal of both intrinsic and acquired GEM resistance in PDAC treatment.

Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex against triple negative mammary carcinoma.

A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non‑platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo.

Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.

Despite significant treatment efforts, pancreatic ductal adenocarcinoma (PDAC), the deadliest solid tumor, is still incurable in the preclinical stages due to multifacet stroma, dense desmoplasia, and immune regression. Additionally, tumor heterogeneity and metabolic changes are linked to low grade clinical translational outcomes, which has prompted the investigation of the mechanisms underlying chemoresistance and the creation of effective treatment approaches by selectively targeting genetic pathways. Since targeting upstream molecules in first-line oncogenic signaling pathways typically has little clinical impact, downstream signaling pathways have instead been targeted in both preclinical and clinical studies.