Are you currently (or have you been) in a Clinical Trial?

Cure-ious-I am one of the ones who suggested MSM. I've been taking it for maybe 4 years now. I don't want to sound vain but I get a lot of compliments on my hair ☺️and I wonder if it has had other positive effects on my cancer. Who knows? I'm still alive and kicking so it can't be hurting me too much.

I sure could use a beer, haha, but my liver wouldn't appreciate it!

Thanks, @cure-ious Yup, we gotta win sometimes! :)

Cure-ious-I tried collagen before MSM. It did nothing for my hair or nails. I put MSM fast dissolving crystals in water. It is the first thing I drink every morning. It took about 6 months for me to notice improvement in my hair but it has made a great difference. New hair obviously has to grow and that's why it takes time to see results. My ALT and AST levels are very good.

When I need to move to a wig I plan on getting something like the woman boss in Night Agent. She has fairly long grey hair-I read an interview where she said it was a wig and thought-Aha-that's what I'll do when the time comes. But hopefully that won't be for a while.

My nails are still a disaster-I need to keep them very short because they crack off. They are not as bad in the summer but really bad in the winter. Maybe collagen would work for you but I was very disappointed.

@chicagoan - where do you buy the MSM fast dissolving crystals supplement? I need to try something for my hair :/

Good news continues so far on the KAT6/CDK4 trial I am on. Tumor markers plummeted after 4 weeks and continue to decline. CA27-29 almost normal at 46. Liver mets are smaller and bone mets started to respond at about 4 months. SEs are minimal, mostly fatigue, I nap daily. I can do most activities, just need to pace myself! Taste is off, especially for salt. Eyes very dry but recently found some eyedrops that seems to be helping. But my finger nails are the best they have been since I was originally diagnosed!

Here is the trial information: https://clinicaltrials.gov/study/NCT04606446

It is so great to see activity on this string again! I always learn so much from everyone.

Cure-ious - what a remarkable response to an unconventional combination! Hoping it continues for you for a very long time!!

jsniffs - how are you doing on the taxol+capivasertib? I too have the AKT1 mutation and my ER+ moved from 95% to 10% and HER2 from 2 to 1. So guessing if we cant target the AKT1 at some point I will also be triple negative.

Lauren - Wow, congratulations! Sounds like you have a great oncologist!

Wow @perky2020 !! Such great news! Gotta love those tumor marker drops!

Thanks for the link to the trial - it's available in San Antonio and Houston for me, so this will be the first thing I ask about when the time comes. So thrilled it's working for you!!

The Halaven is still working—tumor markers dropped another 350, so I'm at 450 from a high of 1200. Far from normal but headed in the right direction. Trying not to get too excited and my hopes up for a long stretch and just going from blood test to blood test. :)

Best to everyone!

Lauren

Hey Perky, there is a report out from last month in Nature Medicine (v highly-rated journal; data must be very good) about your trial!!!

Abstract

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the
safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2−)metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3–4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144–fulvestrant combination (n = 43),the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2–46.1%) and the median PFS was 10.7 (5.3–not evaluable*) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER+HER2− mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446.

• not evaluable= means some people are still on the drug for longer than the 10.7 months, how long have you been on this?
• When they are already getting good numbers for PFS in a phase 1 trial, you know its promising…

https://www.nature.com/articles/s41591-024-03060-0

Hi All. I've been off the boards ever since the decision to possibly leave the RLY-2608 trial (targeted PIK3CA drug). Just needed to take a break, clear my head, and distract myself with life. The two marker liver lesions were growing in very small margins, bone scans are stable but TMs going up quite a bit. I stayed on the trial for a few more months but last week, despite fairly stable scans, MO and I decided to switch to Truqap. Interestingly, my last Guardant showed the PIk3ca mutation was higher than before and the ESR1 mutation disappeared (although from what I gathered from discussion with MO, the fact that I had an ESR1 mutation before may affect treatment choices? Perhaps going back to another AI may not be as effective since the mutation was there and "disappeared" as opposed to never having ESR1?? Not sure but have that on notes to discuss again).

Waiting for Guardant results before final decision on Truqap but that seems to be the likely next step. I'm so saddened by news of RK2020. I never did respond to her comment. So many losses of loving and generous people on this board. And to see the news about Shannen Dougherty just made this a very somber day. Her podcast on MBC was very intense, raw, and honest. I think she was ER+ (same as me). I'm off treatment until Guardant result comes in (hopefully next week) so I'm trying to savor being free of SEs but it's been a gray week and there's that dreaded thought that always comes up when something stops working. . . Thanks for listening and hope everyone is staying well.

In the figure below, you see Celebrex blocks PDK1 upstream of AKT:

Thanks so much, Cure-ious. I was on the trial for about 21 months. Quite good and I'm grateful. Thanks also for the Celebrex info. I read your posts about the Faslodex, Celebrex, Enobosarm with great interest. I will definitely look into getting Celebrex. Really appreciate it.

@cure-ious, just curious (no joke intended), did you already have a script for celebrex or did you have to convince your MO to prescribe it off-label for the PI3KCA mutation?

My wife, so far, doesn't have that mutation but I like to keep options in the back of my head in case we ever get there. She recently asked her MO for a celebrex script just for joint pain as she has been having "trigger finger" in her ring finger which is usually pretty well associated with estrogen deprivation, but he told her it could damage the liver and prescribed some exercises instead to relieve inflammation of the fascia.

BigHubs, Also melatonin can be a good inhibitor of Pi3KCA, and I bet you the best would be these new weight loss drugs, like Ozempic- not tested for cancer yet but do inhibit PI3KCA in the lab, and have positive effects on organs

chicagoan, Its just one paper in the literature where they mixed the drugs and they didn't get a benefit over either alone, so thats far from knowing what they might do in the body. If your TMs are sensitive to the cancer, then you could drop the Celebrex for a month and see what happens. I had to drop Celebrex becuase it caused my creatine levels to go up, and I have one kidney that doesnt function well, so it like aspirin and NSAIDs can damage kidneys. i think the new Ozempic type drugs might do the trick for Pi3KCA cancers too, and they are protective of kidney. However, I haven't seen any paper where that category of drug has been tested for potential anti-cancer activity.

Dear Cureious and others, sorry, I was away. I have asked about Celebrex because some years ago when my wife had a surgery we were advised by one scientist to take Celebrex before, during and after surgery to, sort of, control the inflammation… Now we can see that this drug also interferes with PIK3CA pathway which is a very interesting thing. Hugs,

Saulius

Dear cureious, hmm, that is interesting - so many drugs could interline in different diseases. Some years ago the topic "repurposing" was heard more but now I do not read much about that:/ Your example of Ozempic-type reminds me of metformin. My Sandra still takes 500 mg Metformin for one month and then one month off for many years already. We do not know if it does something for her but metformin being able to inhibit several pathways is well known, and taking it might seem logical because she had liver disease… anyway, maybe one day we'll get some repurposed drugs like in APLeukemia story where some sort of vitamin A or its derivative is used to achieve cures and one scientist, if I remember well, noticed it because one arm of clinical trial used to eat more carrots… crazy:)