Has anyone heard about the target drugs for this master regulator of cancer pathways, called Hedgehog (Hh)?
I read some interesting data presented by William Matsui(John Hopkins) where he basically found that most of the agents we have today are effective against plasma cells but not B cells. And that it is the B cells that are responsible for relapse as they are the ones regrowing the cancerous cells in multiple myeloma not the plasma cells.
I understand there is a drug Zerumbone that is an Hh inhibitor but I have not been able to find anything here at the Beacon on this.,
I found one study but in was in solid tumors and used in combination with lenalidomide and bortezomib at the University of Michigan, the researcher was Dlugosz...he saw dramatic reductions in tumors.
Just wondering if anyone knows where I might locate more on the Phase, II trials done in 2008 that have used Hh inhibitors or more up to date news
Thanks for your time.
Forums
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Re: Hedgehog signaling Pathway
The Hedgehog (Hh) signaling pathway is active in our cells during normal embryonic development, but then usually turned off in adult tissues. However there is now a lot of evidence that this pathway is abnormally activated in a number of cancers, including myeloma, and particularly may be important in keeping alive "cancer stem cells", which may be responsible for relapse, as you suggest below. So this is a very interesting and exciting new approach to treating cancer, and certainly worth keeping an eye on.
Dr. Matsui has written several articles about this subject - one recent one you could look at for more information was in the journal Clinical Cancer Research in June 15 2010 (page 3130), http://clincancerres.aacrjournals.org/content/16/12/3130.long.
Several companies are developing Hh pathway inhibitors and some of these are now in clinical trials for a variety of tumor types: GDC-0449, BMS-833923, IPI-926, LDE-225. None of these are FDA-approved yet however or widely available. GDC-0449 is the farthest along and has shown very promising activity in a type of skin cancer called basal cell carcinoma, and a rare tumor called medulloblastoma. There is a trial of GDC-0449 in myeloma patients open at Johns Hopkins and University of Maryland, though we don't have any results yet from this.
Here's the link for more information for this trial:
http://clinicaltrials.gov/ct2/show/NCT01330173.
Zerumbone is a natural product derived from tropical ginger that is being studied in the lab against several cancers, but I'm not aware of any clinical trials yet with this agent.
I hope this is helpful.
Best,
Adam C.
Dr. Matsui has written several articles about this subject - one recent one you could look at for more information was in the journal Clinical Cancer Research in June 15 2010 (page 3130), http://clincancerres.aacrjournals.org/content/16/12/3130.long.
Several companies are developing Hh pathway inhibitors and some of these are now in clinical trials for a variety of tumor types: GDC-0449, BMS-833923, IPI-926, LDE-225. None of these are FDA-approved yet however or widely available. GDC-0449 is the farthest along and has shown very promising activity in a type of skin cancer called basal cell carcinoma, and a rare tumor called medulloblastoma. There is a trial of GDC-0449 in myeloma patients open at Johns Hopkins and University of Maryland, though we don't have any results yet from this.
Here's the link for more information for this trial:
http://clinicaltrials.gov/ct2/show/NCT01330173.
Zerumbone is a natural product derived from tropical ginger that is being studied in the lab against several cancers, but I'm not aware of any clinical trials yet with this agent.
I hope this is helpful.
Best,
Adam C.
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Dr. Adam Cohen - Name: Adam D. Cohen, M.D.
Beacon Medical Advisor
Re: Hedgehog signaling Pathway
Thank you so much Dr Cohen, or Adam if you prefer.
I was unaware of the trial at John Hopkins, as a newly diagnosed patient I am busy trying to determine which therapy I want for induction.
This involves a very complex decision tree and or algorithm when it comes to drugs,as you know.
While I understand that VLD is the standard of care at the moment for newly dx multiple myeloma, it's not my first choice.
My preference is to switch out the bortezomib for carfilzomib and the lenalidomide for pomalidomide based primarily on the toxicity profiles of pomalidomide, lower myelosupression and the carfilzomib having less peripheral neuropathy, while also binding irreversibly to the cell vs bortezomib.
Is there a way for patients to select their own therapy, when the drug is FDA approved, but does not yet have an indication, for the newly diagnosed? Is it just a matter of finding the right M.D. willing to use the agents off label, like the majority of use for chemotherapy, is?
It frustrates me that the newer less toxic agents are not first line "standard of care" therapy, as well, for newly Dx multiple myeloma patients. After all, given that resistance is a problem, I feel new patients should get to select what therapeutic combination they want particularly, if the toxicities are lower and there is demonstrated efficacy in refractory multiple myeloma patients.
Unfortunately, I have been unable to locate any clinical trials that use carfilzomib in combination with pomalidimde and dex, let alone one that includes new multiple myeloma pts, are you aware of any? I sometimes suspect this is part of big pharmas maximizing their profitable revenues by only allowing access after spending a boat load of money on the other combo, NOW you get the new combo and spend even MORE money. That's a real financial windfall for big pharma...but I digress.
In the course of my search, for my preferred therapeutic regimen, I became aware of the Hh pathway and found Matsui's data exceptionally exciting in terms of targeted drug therapy. I was not aware of the trial at Hopkins with a Hedgehog inhibitor in multiple myeloma pts. thank you for that new information. I plan to read this information along with that on other agents that are still have alphabetic and numeric names which you mentioned. It sounds like an exciting way to start my day learning more about the innovative targeted therapies in the pipeline.
I am very happy to hear that Genetech's trials with Hedgehog inhibitors had success, yet I am disappointed that they did not chose multiple myeloma as one of the cancer's for their initial clinical trials.
Again, thank you for your reply as the news is even more promising that we are approaching not just being multiple myeloma survivors but there is a chance for not only long term maintenance but perhaps to be disease-free in 3-5 years with the new agents. WhooPEE!!
I am more than prayerful that William Matsui will be to multiple myeloma what David Ho was to AIDS, based on his initial research his scientific inquistivenous runs down pathways others have yet to conceive, or explore...and more importantly they challenge conventional therapeutic outcomes based on a far specificity to attach the multiple myeloma mutant stem cell.
O Happy DAY!
You brought joy to my morning.
I was unaware of the trial at John Hopkins, as a newly diagnosed patient I am busy trying to determine which therapy I want for induction.
This involves a very complex decision tree and or algorithm when it comes to drugs,as you know.
While I understand that VLD is the standard of care at the moment for newly dx multiple myeloma, it's not my first choice.
My preference is to switch out the bortezomib for carfilzomib and the lenalidomide for pomalidomide based primarily on the toxicity profiles of pomalidomide, lower myelosupression and the carfilzomib having less peripheral neuropathy, while also binding irreversibly to the cell vs bortezomib.
Is there a way for patients to select their own therapy, when the drug is FDA approved, but does not yet have an indication, for the newly diagnosed? Is it just a matter of finding the right M.D. willing to use the agents off label, like the majority of use for chemotherapy, is?
It frustrates me that the newer less toxic agents are not first line "standard of care" therapy, as well, for newly Dx multiple myeloma patients. After all, given that resistance is a problem, I feel new patients should get to select what therapeutic combination they want particularly, if the toxicities are lower and there is demonstrated efficacy in refractory multiple myeloma patients.
Unfortunately, I have been unable to locate any clinical trials that use carfilzomib in combination with pomalidimde and dex, let alone one that includes new multiple myeloma pts, are you aware of any? I sometimes suspect this is part of big pharmas maximizing their profitable revenues by only allowing access after spending a boat load of money on the other combo, NOW you get the new combo and spend even MORE money. That's a real financial windfall for big pharma...but I digress.
In the course of my search, for my preferred therapeutic regimen, I became aware of the Hh pathway and found Matsui's data exceptionally exciting in terms of targeted drug therapy. I was not aware of the trial at Hopkins with a Hedgehog inhibitor in multiple myeloma pts. thank you for that new information. I plan to read this information along with that on other agents that are still have alphabetic and numeric names which you mentioned. It sounds like an exciting way to start my day learning more about the innovative targeted therapies in the pipeline.
I am very happy to hear that Genetech's trials with Hedgehog inhibitors had success, yet I am disappointed that they did not chose multiple myeloma as one of the cancer's for their initial clinical trials.
Again, thank you for your reply as the news is even more promising that we are approaching not just being multiple myeloma survivors but there is a chance for not only long term maintenance but perhaps to be disease-free in 3-5 years with the new agents. WhooPEE!!
I am more than prayerful that William Matsui will be to multiple myeloma what David Ho was to AIDS, based on his initial research his scientific inquistivenous runs down pathways others have yet to conceive, or explore...and more importantly they challenge conventional therapeutic outcomes based on a far specificity to attach the multiple myeloma mutant stem cell.
O Happy DAY!
You brought joy to my morning.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Hedgehog signaling Pathway
Hi suzierose, I'm impressed by your myeloma knowledge already. How recently were you diagnosed?
You're right that if a drug is FDA approved then physicians have the right to use the drug as they see fit even if it's not officially approved for newly diagnosed patients. In myeloma though this mostly applies to Revlimid, which according to the FDA is supposed to be used only after having tried at least one other myeloma therapy. I think Revlimid is pretty commonly used for the newly diagnosed though. Sometimes an insurance company will only pay for Revlimid if used according to FDA approval, then physicians can sometimes get around this by putting the person on Velcade and/or dex for a brief while and then add the Revlimid shortly after.
The issue with what you'd like to do is that carfilzomib and pomalidomide aren't approved by the FDA--for anything. So a physician, even if he'd like to, can't prescribe them. They only way to get them is through a clinical trial--in which you have to follow their protocol--or maybe each of the pharma companies have set up some sort of patient access program giving access to the drug to certain patients before the drug is approved, but that's usually only available to patients who have run out of all other treatment options--certainly not people who are newly diagnosed.
That's my understanding anyway. Good luck!
You're right that if a drug is FDA approved then physicians have the right to use the drug as they see fit even if it's not officially approved for newly diagnosed patients. In myeloma though this mostly applies to Revlimid, which according to the FDA is supposed to be used only after having tried at least one other myeloma therapy. I think Revlimid is pretty commonly used for the newly diagnosed though. Sometimes an insurance company will only pay for Revlimid if used according to FDA approval, then physicians can sometimes get around this by putting the person on Velcade and/or dex for a brief while and then add the Revlimid shortly after.
The issue with what you'd like to do is that carfilzomib and pomalidomide aren't approved by the FDA--for anything. So a physician, even if he'd like to, can't prescribe them. They only way to get them is through a clinical trial--in which you have to follow their protocol--or maybe each of the pharma companies have set up some sort of patient access program giving access to the drug to certain patients before the drug is approved, but that's usually only available to patients who have run out of all other treatment options--certainly not people who are newly diagnosed.
That's my understanding anyway. Good luck!
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Penny
4 posts
• Page 1 of 1