Does anyone have any insights into any therapies or potential therapies that involve the inhibition of PHGDH via NCT-503? From my understanding of articles I have found, inhibition of PHGDH (phosphoglycerate dehydrogenase) slows the growth of melanoma. The most effective pharmacologic inhibitor is with NCT-503. (Journal of Investigative Dermatology (2020) Volume 140).
- May 3, 2021 at 1:03 pm
I am curious to know whether if this therapy has been utilized and if so, would it be supplemental to immunotherapy (Opdivo).
The articles I have read are far above my level of education, but what I can understand, it seems like a very promising therapy.
If there is anything that can lower the possibility of metastasis, I’m all for it!
Hi Glenn Beck, so after a little reading and digging I will share two articles with you and I would suggest going to the conclusion or discussion sections of the articles. What I found is an interesting target in many cancers in the research department so far but no drug(s) has been developed or tested on humans yet. Maybe in the future but for now it would fall in the big bucket of possible approaches being studied in labs, next step mice and then one day humans. Here are the links. https://www.ijbs.com/v16p1495.htm https://www.nature.com/articles/s41420-021-00474-4
- May 3, 2021 at 1:40 pm
If you really want to go down the rabbit hole, another of these pathways (kynurenine) was studied and is still being looked at even after the monster failure of Keynote 252/ECHO-301 of Epacadostat+ pembro an IDO inhibitor. Here are two articles that look at the big picture and IDO specific. https://www.annualreviews.org/doi/full/10.1146/annurev-cancerbio-030419-033635 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30274-8/fulltext
- May 3, 2021 at 2:08 pm
Thanks, Ed. I had previously found the two articles you linked in your first post. The information is fairly fresh, but I was curious if anyone else had discussions regarding this potential therapy.
- May 3, 2021 at 3:01 pm
I was unaware of the trials referred in your second post. I guess it shows that promising theories do not always produce the results that are sought.
I will continue to search for more information and remain optimistic.
The IDO inhibitors were the hot area of research after Ipi+nivo was approved and started an arms race between Merck and Bristol Mayer Squibb with both companies buying smaller companies for big $$$ only to rush from phase one to phase three trials only to find the Merck trial failed and all research was shut down across the board with big $$$ losses!!! The drugs closest to approvals or trial finishing would be Lag-3, NKTR-214 a version of the old IL2 drug, Iovance LN-144 TIL’s program and maybe TLR9 agonist. The next wave after these looks to be bispecifics and ways to get immunotherapy drugs to target without the toxicity or less toxicity. dr. Jason Luke and Dr. Omid Hamid are melanoma experts and if you look them up on Twitter, you will find they are always posting about the latest areas of research in melanoma and other solid tumor types. If you go to Feb.26 post by Jenn Silverman on Dr. Luke’s Twitter account , you will find a really interesting presentation by him. He covers all the areas of research in melanoma in detail. https://twitter.com/jasonlukemd?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor
- May 3, 2021 at 4:34 pm
tim brownParticipantInteresting conversation. I’m nowhere near as well read or knowledgeable as Ed, but I read an interesting criticism of the clinical trial process when the novel checkpoint drug or combo fails, which has sadly been the case recently.
- May 4, 2021 at 9:10 am
The writer, a European melanoma researcher / oncologist demanded that the details of the ‘failures’ be made known rather than simply buried so that lessons could be learned. Pie in the sky?
BubblesParticipantAmen and Amen, Tim!!! Edster is a master researcher. AND….though a phase 1 clinical trial saved my life….there is much that needs to be improved in the system. Here are just a few of my thoughts, and rants, on the subject if you are interested ~ https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2020/01/clinical-trials-lies-damn-lies-and.html
- May 4, 2021 at 10:01 am
My best to all. celeste
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