June 22, 2012
Promising Pancreatic Cancer Treatment
(Ivanhoe Newswire) — There are more than 42 thousand new diagnosed cases of pancreatic cancer in the U.S., and of those, more than 35 thousand have resulted in death. Now researchers are looking at a new treatment that could change how we view pancreatic cancer.
A novel chemotherapeutic agent, the highly selective MEK1/2 inhibitor BAY 86-9766, may be a promising future treatment for pancreatic ductal adenocarcinoma (PDAC). In a preclinical therapeutic study, BAY 86-9766 was evaluated in one of the most aggressive mouse models for PDAC. The researchers induced endogenous genetic alterations in these mice, and within eight weeks, the mice developed invasive, lethal PDAC. These genetic alterations closely mimic what is found in most human cases of the disease.Nicole Teichmann, Ph.D., of the Klinikum rechts der Isar at the Technische UniversitÃ¤t MÃ¼nchen in Munich, Germany was quoted as saying, "We showed in our endogenous mouse model that our novel chemotherapeutic agent leads to dramatic tumor shrinkage after only one week of treatment. Moreover, the therapy was as effective in animals with advanced tumors and ascites, which is often the case if patients come to the clinic."
A daily treatment of 25 mg/kg with BAY 86-9766 prolonged the survival of the mice in the study compared to their 'placebo'-treated counterparts; median survival advantage was 20 days. The treatment caused dramatic tumor regression after only one week and was effective in animals with advanced tumors and ascites, which is often how patients present to the clinic. "We were really surprised that the tumor load dramatically decreases after one week of therapy and also that the treatment conferred such a strong overall survival benefit. In our hands, this is the first targeted drug to have shown such strong tumor effects in an endogenous mouse model of PDAC," Teichmann was quoted as saying about the results.
In most animals, the tumor relapsed after three weeks of treatment, which modeled the situation in humans. "Often patients respond to a therapy and after a while, the tumor relapses," she added. "We can exploit this same tumor relapse in the mouse to investigate the resistance mechanism to improve the therapeutic strategy."
"The mutations trigger the onset of a signaling cascade that is necessary for the survival and proliferation of the cancer cells," Teichmann explained. "Our novel chemotherapeutic drug inhibits one essential protein of this cascade and therefore leads to the cascade's shutdown."
These findings encourage testing in mouse models rather than xenograft models. "Our results support testing novel agents for pancreatic cancer in endogenous mouse models, rather than conventional xenograft models because they take into account the genetic and morphological heterogeneity of the disease and may be more predictive with regard to efficacy," Teichmann concluded.
SOURCE: American Association for Cancer Research June 2012