Researchers from Virginia Commonwealth university have developed a new therapy by combining a common antibiotic and experimental drug to cure pancreatic cancer. This study was published in Cancer research.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer that is predicted to cause almost 40,000 deaths in the United States in 2014. PDAC is faily resistant to most standard therapies and results in a 5-year survival rate of about 4%.

The aggressive nature and dismal prognosis of patients with pancreatic cancer results partly from the plethora of molecular changes that occur during PDAC development, one of which is overexpression of the antiapoptotic proteins of the Bcl-2 family. Cancer cells exploit this overexpression to evade cell death and as a mechanism promoting resistance to diverse chemotherapeutic agents.

Sabutoclax (BI-97C1) is a novel Apogossypol derivative BH3 mimetic. This compound binds to the Bcl-2 antiapoptotic proteins Bcl-2, Mcl-1, BclXL, and Bfl-1. It was originally identified on the basis of its ability to bind Bcl-XL with low to submicromolar binding affinity . Scientists have previously shown that sabutoclax shows efficacy against prostate and colorectal cancers, two cancers that also overexpress antiapoptotic Bcl-2 proteins

In this study, researchers offer evidence of the combinatorial antitumor potency of these agents in several preclinical models of pancreatic cancer. Sabutoclax induced growth arrest and apoptosis in pancreatic cancer cells and synergized with minocycline to yield a robust mitochondria-mediated caspase-dependent cytotoxicity. This combinatorial property relied upon loss of phosphorylated Stat3 insofar as reintroduction of activated Stat3-rescued cells from toxicity. Tumor growth was inhibited potently in both immune-deficient and immune-competent models with evidence of extended survival.

Their results showed that the combination of sabutoclax and minocycline was highly cytotoxic to pancreatic cancer cells and safely efficacious in vivo.