A treatment for highly aggressive and commonly fatal pancreatic cancer is being developed, reports a University of Houston researcher who has designed a new medicine that can inhibit two of the major pathways of the deadly disease.
Ruiwen Zhang, MD, PhD, and Robert L Boblitt, Endowed Professor in Drug Discovery, have published findings, along with Research Associate Professor of Pharmacology, Wei Wang, MD, PhD, in Cancer Research Journal.
‘There is an unmet clinical need for new, effective, and safe drugs for pancreatic cancer therapy. Our discovery represents a significant advance in cancer research,’ said Zhang.
‘Most drugs only target one factor. We identified a single compound that targets two linked genes that cause cancer.’
The drug would be a first-in-class, new therapy for pancreatic cancer, and a new conceptual framework for developing other drugs.
The two cancer-causing genes linked in pancreatic cancer are nuclear factor of activated T cells1 (NFAT1) and murine double minute 2 (MDM2), a gene that regulates (and depletes) the tumour suppressor gene called p53. If there is no tumour suppressor p53 present, MDM2 will cause cancer on its own. NFAT1 up-regulates MDM2 expression and encourages tumour growth.
‘We developed a synthetic compound that we call MA242, and it can deplete both proteins at the same time increasing specificity and efficiency of tumour killing,’ remarked Zhang.
‘In our molecular modelling study, MA242 is a potent dual inhibitor.’
Though it is man-made, the new compound is based on a type of sea sponge.
Patients with pancreatic cancer have too much MDM2 and NFAT1, which has left these genes as open targets for cancer therapy. Numerous studies have shown reduced MDM2 can lead to decreased tumour growth and progression.
Heathy individuals have low levels of MDM2 and NFAT1, but diet, nutrition and environment can cause higher levels in cells, said Zhang. In previously published work, Zhang revealed that certain natural foods and products, like broccoli, soybeans, green tea and turmeric, have shown potential for cancer prevention and therapy.