Pancreatic cancer therapy and diagnosis
The current disclosure relates to methods for treating pancreatic cancer or chronic pancreatitis in a subject comprising administering an antagonist of a dopamine receptor to the subject wherein the dopamine receptor is, in some specific cases dopamine receptor D2 (DRD2). The antagonist in some specific cases is an RNAi construct, an antibody, or a small molecule and in more specific cases pimozide or L-741,626. The disclosure also relates to diagnostic methods comprising the detection of the expression of DRD2 in pancreatic tissue and kits for doing the same.
1. A method for treating pancreatic ductal adenocarcinoma or chronic pancreatitis in a subject in need thereof, said method comprising administering an antagonist of a dopamine receptor to the subject, wherein the antagonist of the dopamine receptor is selected from the group consisting of pimozide and L-741,626.
2. The method of claim 1 , wherein said antagonist is pimozide.
3. The method of claim 2 , wherein pimozide is administered in dosages of between about 0.01 to 5 mg/kg body weight/day.
4. The method of claim 3 , wherein pimozide is administered in A dosages of about 0.2 mg/kg body weight/day.
5. The method of claim 3 , wherein pimozide is administered orally.
6. The method of claim 1 , wherein said antagonist is administered in combination with gemcitabine.
7. A combination for treatment of pancreatic ductal adenocarcinoma or chronic pancreatitis, comprising an antagonist of a dopamine receptor, together with at least one additional anti-cancer drug, wherein the antagonist of a dopamine receptor is selected from the group consisting of pimozide and L-741,626 and the additional anticancer drug is gemcitabine.
8. The combination of claim 7 , wherein the antagonist is pimozide.
9. The combination of claim 8 , wherein pimozide is provided in dosages of between about 0.01 to 5 mg/kg body weight/day.
10. A diagnostic method for detecting chronic pancreatitis or pancreatic ductal adenocarcinoma cells in a subject, comprising
providing a biological sample derived from the pancreas of said subject,
detecting the presence or absence of dopamine receptor D2 (DRD2) in said biological sample,
wherein the presence of DRD2 in said biological sample is indicative for the presence of pancreatic tumor cells or chronic pancreatitis.
11. The method of claim 10 , wherein said biological sample is a pancreatic tissue sample.
12. The method of claim 10 , wherein said sample is an immersion fixed paraffin embedded tissue sample.
13. The method of claim 10 , wherein in step b. DRD2 is detected directly or indirectly by detecting DRD2 Mrna expression.