Targeting dopamine receptor D2 to inhibit cancer cell proliferation in PDAC patients
A novel PDAC biomarker has been identified at McGill University, along with the use of pharmacological inhibitory molecules as a new PDAC treatment.
For patients with pancreatic ductal adenocarcinoma (PDAC), combination chemotherapy is only moderately effective at extending the median disease-free survival rate. In order to expand treatment options, variations in the DNA and RNA of PDAC samples have been studied at a genome-wide level. This provides an opportunity to investigate molecular subtypes of the disease and then provide tailored treatments to patients. From those molecular datasets, dopamine receptor D2 (DRD2) was recently established as a crucial protein for pancreatic cancer cell survival and potentially a novel target for PDAC treatment.
This invention describes the novel use of DRD2 antagonists (including FDA-approved Pimozide) as therapeutics for PDAC treatment, as well as the use of DRD2 as a PDAC-specific biomarker. Previously approved for neurological disorders, pimozide and haloperidol can now be used in a drug-repositioning strategy. RNA interference knockdown of DRD2 or inhibition with pharmacologic antagonists reduced proliferation of pancreatic cancer cells and cell migration. Furthermore, administration of the DRD2 inhibitor haloperidol to mice with orthotopic xenograft tumors reduced metastasis and final tumor size.
- FDA-approved drugs reduce proliferation of pancreatic cancer cells and metastasis in PDAC mouse models
- DRD2 is a novel biomarker for the most common type of pancreatic cancer: pancreatic ductal adenocarcinoma
Filed US, EP, CA