NEWS Dec 1st: CC researchers target *stem* cancer cells

[GrouseMan]

Maia and Grouseman, thank you so much for the great information. I don't understand a lot of it but am always so edified that there is so much knowledge available for those who have an interest.

Grouseman, your explanation of drug development is very enlightening, but also somewhat discouraging, I think, for those who are being treated now. The time frame is so long, it seems, that many who are in treatment now will have run out of options before a new drug that looks promising may be available. And then of course there are the many things like you mentioned that look so promising in the beginning but insurmountable obstacles prevent them from ever being viable treatment options. Can't imagine how difficult that must be for those who are trying to develop these new treatments.

Laurettas,

Yes - It was a very difficult job made all the harder when the programs were shuttered by new management. (I am still very bitter and angry about it) Un-like other therapeutic areas of research for which there are many drugs and treatments available and people may never be terminal in the same sense that cancer patients are, it can be very hard on the researchers. I have had many acquaintances, and friends that have lost loved ones. Its hard to look them in the face or even offer condolences when you think that had we worked harder or faster, or had more money to hire more people, perhaps we might have had something available that could have helped their loved one.

Now I find myself in the exact same boat with my wife, and I am ABSOLUTELY helpless to do much more than keep a watch on what is happening and help her to make good decisions. I look all the time for any edge I can, the lead time is very long. It doesn't help at all with these news articles boasting about this that or another breakthrough, at best In Mice! 10s of thousands of treatments of all kinds, not just in cancer, that have looked great in a preclinical situation never got further than that. I am sorry - one should never give up hope. I am a pessimist by nature. Always have been. They say a pessimist is just an optimist that has been disappointed too many times. As a result because of the ironic nature of what the universe has thrown at us, I am having a VERY difficult time with my wife's situation. I don't know how many times I talked about early detection. We eat healthy. She was a distance trail runner. Doctor should have been more forceful 3 years earlier to get that first colonoscopy. But everyone thought there was no risk! How very wrong.

Anyway - I come here to attempt to help people understand as much as they can about the drugs they are taking, and those that are coming down the pipe. I think being educated is better than ignorance, and affords better decisions. I check in here to learn as well. What to expect as time goes on. My wife isn't much on talking about this disease, even to me. She is really trying her best to forget about it, living her life as she always has for as long as she can I guess. But we are pragmatists. Her cancer had spread too far by the time it was discovered. Mets to the spleen, liver and lungs! No one will offer any kind of further surgical intervention to her at this point. She isn't even interested in a second opinion right now and I can't force her to do it! Having worked in the industry I know a lot of researchers still. I can get really good opinions on treatment plans etc from some pretty brilliant people. But for all that am still helpless if the treatments are just not there yet.

Sorry - hard to deal... work sucks. It's not what I want to do for a living right now. I wish I could have continued what I was doing but at my age its impossible to find employment when up against young folks that will work for a lot less money, and don't care if its not a career. 10's of thousands of drug researchers have lost their jobs over the last 7 years due to pharmaceutical companies down sizing and moving research to China. Most are now under employed, early retired not by choice or working jobs that are very different than they thought they would ever be in.

GrouseMan

[GrouseMan]

Thank you both for sharing this hopeful research!
Grouseman, so is this Phase 3 trial compound something you think might impact current patients soon? Where is this trial? It sounds very exciting!

Jane

Here is a link to a list of trials in progress for Dacomitinib (also known as PF-00299804).

http://clinicaltrials.gov/ct2/results?t ... rch=Search

as you will note they are primarily for NSCLC, for which EGFr Her2, and HER4 are usually overexpressed or have aberrant signaling making NSCLC probably the best clinical test case. If its active against this and is better than existing protocols (which I think it will be) then its likely to be approved I would guess in the year or two at the most after a successful conclusion of one of these phase III clinical trials, unless the FDA decides they need more data. The Archer 1009 trial looks like the biggest and likely the one that will generate the most conclusive data. They have completed the data collection apparently in September, and expect the results to be completed in August of 2014. I bet we will hear much more about this at the next AACR meeting. I am betting it will get FDA approval likely sometime in 2015 perhaps maybe earlier depending on how fast the FDA moves.

There is another Pfzer drug I am familiar with that is currently fast tracked by the FDA. it is a CDK4,6/Cyclin inhibitor named palbociclib (PD0332991):

http://clinicaltrials.gov/ct2/results?t ... rch=Search

and a third named Xalkori (crizotinib) and c-Met/ALK inhibitor.

http://clinicaltrials.gov/ct2/results?t ... rch=Search

GrouseMan

[Laurettas]

Grouseman, what an extremely difficult position to be in. I hope you are able to divorce yourself from the feeling of any personal responsibility for those who have cancer--even your wife. We are all limited to what the powers that be give to us at this point and we are definitely not in control of anything! I felt a certain burden for my husband as well since, as the internet addict in the family, I knew well that traditional treatment was not going to be helpful for him in any significant manner. I have, I am sure, well over 1000 links to articles discussing treatments and drugs that I thought might be helpful but of course it is impossible to find a doctor with the courage to try these out of the box ideas.

I share your frustration with all of the articles touting some potential advance in treatment. I think we need only look at the paltry advances in colon cancer treatment in the last 50 years to see that most of these "breakthroughs" end up being insignificant or worthless.

I don't know you personally but I would question whether or not you are a pessimist. I have gotten that label but I look at myself as more of a realist. I strive to look at what IS rather than how I WANT things to be. I was accused of having no hope by a friend when I expressed the reality of my husband's situation. Hope that is not supported by reality is delusion, IMHO.

Again, thank you so much for sharing your deep knowledge with us. I am amazed every time I read someone expounding on the complexity of a single cell in our body and long to have that knowledge myself!

[smokeyjoe]

Mia there is a clinical trial ongoing that targets cancer stem cells in Ontario at the Hamilton Health Sciences Centre. BBI608 is the most clinically advanced candidate in Boston Biomedical’s cancer stem cell (CSC) pathway inhibitor program. This first-in-class, orally-administered small molecule blocks CSC self-renewal and induces cell death in CSCs as well as non-stem cancer cells.

Does anyone know anything about this trial?? Side effects, etc.

[Maia]

I do know, smokey. I had big expectations about this since one year ago. For me, it's all about to try immunological approaches AND/OR target *stem* cancer cells.
Two months ago, when my friend failed Folfiri, I've emailed with a researcher there. He told me, despite the trial is listed as recruiting: "unfortunately, our study has no longer been recruiting patients for many months now and the only to access the agent is through the NCIC clinical trial". (He means one could go to other locations). I keep pushing and he replied "Because the drug is as yet unproven, there is no other way of getting it, compassionate or off-label or otherwise. This said, in our experience, although there might be a slowing of tumour growth, we didn't see huge amounts of activity and I sadly doubt this new agent will be a panacea." For obvious reasons, I won't say his name in an open forum.
So, there you go.

BUT, since we are at it... after that, I've checked with the Ottawa Hospital (another treatment site, according with clinicaltrials.gov). They told me there:
"Unfortunately, the BBI608 study that you referred to is not currently open at our site for accrual. The sponsor has decided to place this study on hold for an undetermined period of time while they evaluate other projects with this agent.

We do have an alternate study with the same sponsor and a similar type of agent (cancer stem cell inhibitor) called the BBI503 study."

So I checked and checked for that and they, for starters, admited my friend and emailed the forms and such. But my friend went with her oncolologist and they agreed to do a 3 moths break (after radiation to a lung met that was about the colapse the lung). The break is finishing this week and she' starting Folfox next week (Folfox is second line for her, because she had Folfiri + Avastin as first line).

So, if you're interested in a trial with a stem cells inhibitor, you should check for this agent BBI503 (it looks like it's a better version of BBI608 , right?).

This is the trial: A Phase I Clinical Study of BBI503 in Adult Patients With Advanced Solid Tumors : http://clinicaltrials.gov/ct2/show/NCT01781455

The two only sites are Ottawa Hospital (Canada) and Institute for Translational Oncology Research, Greenville (South Carolina, USA), at the moment.

[Maia]

BTW... it's pill, an oral agent.

[ldomo]

Having been on the BBI5503 trial - believe me it is not a colon cancer cure - it was suppose to target stem cancer cells. I think that is the only thing it didn't kill. After a mere 3 weeks, I pulled out because I couldn't take the side effects that were vicious. Appears like for the risk, I have lost precious time. When it sounds too good... Also when I dropped out at my site in MA, of the 29 in the trial - 8 others had dropped out. not sure if any real results were received with colon cancer.