Gemcitabine plus Cabo in pancreatic cancer and AACR TH-302 data
I know we have discussed the paper that demonstrated robust Cabo plus Gemcitabine efficacy for pancreatic cancer in xenograph models, but I wanted to revisit because the paper could have important implications on Cabo development program. First the title of the paper------- "c-Met Is a Marker of Pancreatic Cancer Stem Cells and Therapeutic Target" ---------- The paper is very busy with data, and I recommend revisiting as it jives with AACR post on TH-302 plus gemcitabine from Sally I will reference later. Gemcitabine is thought to produce a hypoxic environment and induce more cancer stem cells. The paper demonstrates the effects of gemcitabine, cabo, and cabo plus gemcitabine on primary tumors and metastases.
Now Sally highlights another drug in development, TH-302. Sally (MaverickNY) authored -----"Highlights of AACR 2012 part 3"--------- from her Pharmacy Strategy Blog. She goes on to describe a hypoxia activated pro drug, TH-302, in combination with gemcitabine, and effects on cancer stem cells in pancreatic cancer. There is some interesting parallels between TH-302, and Cabo despite different MOA. Despite the differences, the main just is the same. The rationale for combining a drug that attacks gemcitabine resistance from hypoxic environment.
I highly recommend reading the links she references. Sally goes on to state that the scientific idea is worth testing, and that TH-302 may not be the one that gets breakthrough status on the limited results she describes in phase 2b human trials. ----I find the mention of breakthrough status here interesting in that Cabo has a similar active combo trial with gemcitabine in phase 1 that started in July of 2012.
I know Diane Simeone is very involed in cancer stem cells and pancreatic cancer. There is a video of which she talks about xl 184. Go to youtube and type simeone+pancreas. You will see a video called targeting pancreatic cancer stem cells. I have not looked around lately regarding xl 184 and pancreatic but maybe this weekend i will look around to see if i see fresh conversations.
"Hbomb, are you inferring that cabo has a better chance to be designated with a breakthrough status than TH-302 or is less or equally unlikely to gain the breakthrough designation?"
I really didn't infer that Cabo has a better chance, but wanted to point out that Cabo is a player here, and it bears watching. I really don't know what qualifies as breakthrough, but Sally identifies a particular strategy for a drug that targets gemcitabine resistance in hard to treat pancreatic cancers. I agree with her conclusion, that TH-302 is not likely to qualify with results from this limited phase 2 study.