This topic is lockedI’ve been doing a bit of a dive into skin cancer recently, reviewing some of the literature on the usual three types of basal cell carcinoma (BCC), squamous cell carinoma (SCC), and melanoma, but especially the first one. What I find interesting about skin cancer is that (at least prior to metastasis) we have direct access to the tumor, which opens the door to a number of treatments that aren’t possible for internal or systemic cancers.
Because of this fact, the most common treatment for these cancers is surgery. Just cut them out and move on. And usually that works perfectly well.
However, it is probably more useful from the viewpoint of broader cancer research if we could figure out how to eradicate these cancers with topical drugs, supplements, or small molecules alone. The protective skin barrier means that we can apply much higher concentrations of larger and more powerful drugs without anywhere near the same level of systemic side effects. It almost feels like an “easy” version of cancer, that we should be able to beat entirely before moving to the “hard” ones.
So, I wanted to start some discussion on ideas for topical treatments for skin cancer, list what is commonly known, get a feel for what immune-boosting supplements have topical activity, etc.
To start, it appears that the two most commonly prescribed topical treatments are the following:
1) 5-fluorouracil: A chemotherapy drug believed to block the action of thymidylate synthase and thus stop the production of DNA. This is overall a pretty dangerous product, with a small and variable effective dose, that is better used via topical administration.
2) Imiquimod: A topical immunotherapy which yields profound antitumoral activity by stimulating both the innate immune and adaptive immune systems, including NK cells, macrophages and B-lymphocytes. This one feels much more interesting and exciting to me.
There is a third option for BCC growing in popularity which is the anti-fungal itraconazole. Apparently, BCC depends heavily on the hedgehog pathway. However, while oral itraconazole has shown some noteworthy successes, I only found 1 or 2 studies on topical use which found no effects. This could either indicate that itraconazole needs to be metabolized before it can help, or that the topical dosage was too low.
Another relevant point of discussion is NAD+. There have been a series of studies reporting conflicting effects of NAD+ precursors on cancer. Because NAD+ is needed by DNA repair factors such as PARP, it is widely expected that NAD+ would help prevent most forms of cancer (with possible exceptions in certain liver and breast models). Even so, it is also known that many forms of cancer upregulate NAD+ production to use as a metabolic substrate, so that an already established cancer might progress more rapidly through NAD+ supplementation. I came across an excellent longecity post from a few years ago which discusses this interplay in more detail.
Skin cancers are an even more interesting case, as oral NAM supplementation has already shown large positive effects on BCCs in RCTs. This prompts the question as to whether topical NAM supplementation could be even more effective against a tumor. However, NAM is tricky. Its immediate effect is actually to downregulate SIRT1 before gradually upregulating it over a longer period of time. Which of those two effects helps fight the cancer, or are both needed? Topical administration of NAM might downregulate SIRT1 even more aggressively, while topical NR or NAD+ itself would surely upregulate NAD+/SIRT1 even more than NAM. Once the specific effects of NAM are more fully disentangled, I would guess a very robust approach will reveal itself here.
What else is there? I’m sure we all know the classic immune boosters: Vitamin C, Vitamin D, Zinc, Quercetin, Astralagus, EGCG, Garlic/Allicin. I’d imagine most of these have topical activity. Are there any that don’t? Are there any whose topical effects would substantially differ from their systemic ones?
What about topical immune boosting mushrooms like Reishi or Turkey Tail? Topical senolytics like fisetin? Topical iodine? Topical C60?
I’ll leave it there to start. I am very curious to hear any thoughts or experiences people have on any of the above substances in a topical setting, or any other ideas people might have in the realm of topical therapies for skin cancer.
Edited by timedilation, 19 March 2023 - 06:58 PM.
