Blocking pathways and reducing overexpression of oncogenes

Hi everyone, I’m just sharing questions I have for my oncologist as he’s a colorectal cancer researcher. I’ll report back on Jan 6 after my appointment with him. I’m not asking questions to the group - I just can’t be fucked changing it to statements because it’s 35 degrees today, feels like 40 degrees and I’m dying 🤣. Hopefully if you have the same risk factors, this could help guide further research. Also, a 10 year HBOT study shows if

you do it before and after radiation, side effects were reduced or non-existent in 80% of participants (rectal cancer). It’s only subsided for brain cancer patients in Australia and the TGA are cunts here. But if you can get a subsidy, go for it! It also reduces drug resistance and can improve chemo efficacy.

Questions:

Have you had any patients on Rapamycin? I have been looking into this and believe there are early stage clinical trials going on for its use in drug resistant colorectal cancer and specifically its synergistic effects with 5-FU, e.g. inhibits mTOR, increases senescence, decreases thymidylate syntheses and angiogenesis etc.

Have you ever used or researched inhibitors of ABCG2 pumps to reverse MDR1 over-expression? I noticed the cells in the length of my tumour decreased (assuming these are the neoplasmic cells sensitive to capecitabine) but the width snd height have grown quickly, so perhaps these are the more resistant populations.

What is the best way to target VEGF and ANG overexpressions? These are the highest risk factors for angiogenesis that came up on my Onconomics testing, along with FGF, PDGF, and ANG1 and 2. Vabysmo looks promising but can impact eye health.

Have you ever used Avastin as an adjunct outside of its use along side other immunotherapy drugs to block VEGF? I have 35% sensitivity to this and there’s promising data when used with chemo or metabolic therapy and HBOT, but Keytruda, Opdivo and Yervoy were completely useless for me because I have normal expression of MMR genes and no MMR deficiency.

Which inhibitors of topoisomerase and nucleoside analogues in your experience have least side effects out of Doxorubicin, Ironotecan, FUDR and UFT? I want to plan for all scenarios if my tumour continues to grow after returning to the ReDO protocol and a strict ketogenic diet. I will consider using one of these with a low dose, under fasting conditions and with HBOT.

Which alkylating agents out of Cisplatin, Carboplatin and Oxaliplatin do you most commonly recommend in the context of colorectal cancer? These have come up as high sensitivity in my drug testing, but have quite a range of side effects. I will only consider these if I can have a very low dose, under fasting conditions and with HBOT.

Have you ever used any adjuncts with 5-FU and/or capecitabine to reduce elevated RNR activity and enzymes that impact my cells’ sensitivity and resistance? E.g. I have NP, TS, DPD and PS and they deactivate up to 80% of the drug so maybe that’s why it hasn’t worked without repurposed drugs, e.g. ivermectin and Fenbendazol improve sensitivity to 5FU. Also, Cimetidine being an H2-receptor antagonist inhibits liver enzymes and allow for higher concentrations of 5FU to enter the tumour-micro environment (but this can also lead to toxicity)

Should I consider HER1 and EGF blockers like Iressa, Tykerb or Tarceva? These are more used in breast cancer but I didn't realise this was a high risk proliferation stimuli for me until I reread my drug sensitivity data.

How can risk factors for migration invasion be managed, e.g I have highly overactive MMP and 67LR? So far I’ve only seen data on EGCG and a drug in early clinical trial stages - Marimastat

Does heating extracts impact their active compounds? I’ve started taking Dandelion root extract and the data is absolutely amazing in colorectal cancer studies. I put it in tea and maybe the hot water is destroying the compounds. Specifically these are Taraxasterol, α-amyrin and β-amyrin, Lupeol, Phenolic Acids and Flavonoids such as chlorogenic acid, chicoric acid, caffeic acid, and luteolin. It’s an amazing adjunct but the studies don’t specify how patients took it, e.g. straight, in cold water, hot water, etc.

Have you ever done any research on addressing MDR1 and MRPs? These are regulated by 35% and 45% in my cancer cells, so perhaps this is why capecitabine did not prevent disease progression this time around on its own (I took higher dosages than before but without ReDO drugs).

Do you know much about the role of DNA methylation? This is new to me and 06-methyl-DNA-tran was flagged as a 30% risk factor for me, but I only just noted this down.

Should I be concerned about elevated PARP (1-17)? I have this and I read in some studies that it is associated with increased aggression of cancer cells when exposed to chemo agents.

What role does regulation of apoptosis play? I have learned recently that Bcl-2 is overexpressed by 20% and CD95 (fas-r) by 40% which is messing up the pro-apoptotic mechanisms, e.g cytochrome being made by the mitochondria. Perhaps this is why my reduction in tumour size was so slow in previous protocols (before the recent progression). CDK4/6 is also overexpressed by a whopping 60%. There are inhibitors for these, but I am either not sensitive to them or they were not tested, e.g. Palbociib, Ribociclib and Abemaciclib.

Are you aware of any studies on T-5224 to inhibit c-Fos and c-Jun signalling pathways (aka AP1s)? These seem to decrease inflammatory cytokines.

Apart from radiation, do you know of any new approaches to exploiting HSP90? My cancer cells are sensitive to this so maybe I can do a hotter sauna that has also has red light therapy.

Apart from Gemcitabine do you know of any RMM1 blockers? Unlike capecitabine, it has a poor oral absorption.

Can you advocate for rectal cancer patients to get HBOT subsidised? As you know, I declined radiation in 2023 due to the location of the tumour and surrounding reproductive organs - radiation of that area would make me infertile and induce early menopause. I was told to have radiation everyday for 5 weeks AND have intravenous chemotherapy, followed by a debulking and colostomy surgery. I felt this was too much! There’s also risk of ulcers, bleeding, chronic diarrhoea, fibrosis, strictures, sexual dysfunction, incontinence, etc. This is why HBOT should be taken seriously by TGA and subsidised for those who have radiation - the research from as early as 2004 to current includes case reports and medium size control trials. The positive effects cannot be disputed anymore - oxygen saturation enhances cancer treatments, reverses hypoxia, increases stem cell production and white blood cells, stimulates re-epithelialization, induces ROS in cancer cells, helps heal tissue damage and improves cognitive function. The list goes on and on!

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