Trump has collapsed cancer research. —> The National Cancer Institute hasn’t made a single grant this fiscal year
Nationally, N.I.H. grants to universities are down by more than ninety per cent in the current fiscal year; during that time, the National Cancer Institute hasn’t made a single grant.
Full story: The Unmaking of the American University (New Yorker)
The analyzed transcript evaluates the complex, frequently paradoxical role of the non-essential amino acids serine and glycine in cancer progression, specifically through their integration into one-carbon metabolism. The core thesis posits that while early clinical interventions utilizing dual serine- and glycine-restricted diets show promise in limiting tumor proliferation, isolated biochemical data indicates that serine is the primary oncogenic driver. Pre-clinical models and in vitro assays demonstrate that serine restriction stunts neoplastic growth, whereas isolated glycine restriction yields negligible anti-tumor efficacy.
Crucially, the transcript identifies glycine as a metabolic “double agent.” Because the enzymatic conversion of serine to glycine via serine hydroxymethyltransferase (SHMT) is substrate-dependent and fully reversible, supraphysiological influxes of exogenous glycine force the pathway backward. This reverse reaction (glycine to serine) consumes, rather than donates, the critical one-carbon units required for nucleotide biosynthesis. Consequently, high intracellular glycine acts as a metabolic sink, starving the tumor of the nucleic acids necessary for DNA synthesis and genomic replication. While pre-clinical murine models suggest high-dose glycine supplementation limits tumor progression by exploiting this bottleneck, severe translational gaps remain. The aggressive leap from in vitro isotope tracing to human oncological protocols is premature, and additional large-scale, randomized human trials are mandatory to determine the safety and efficacy of targeted amino acid modulation in active malignancies.
| Specific Claim | What they cited | Verified status + PubMed/DOI Link | Evidence Grade (A-E) | Verdict |
|---|---|---|---|---|
| Dual restriction of Serine/Glycine reverses cancer mass | Phase I clinical trial data | Verified. Early Phase I data (e.g., ChiCTR2300067929) shows -SG diets modulate systemic immunity and limit tumor proliferation. PMC12708301 | Level C | Plausible |
| Serine restriction inhibits tumor growth; glycine restriction does not | In vitro (cell culture) assays | Verified. Exogenous glycine cannot substitute for serine in driving proliferation because the reverse conversion consumes one-carbon units. PMC12708301 | Level D | Strong Support |
| High glycine reverses one-carbon metabolism, starving cancer of nucleic acids | Isotope tracing in cell models | Verified. Reversing the SHMT reaction drains 5,10-methylene-THF, acting as a one-carbon sink and starving the cell of nucleotides. PMC12708301 | Level D | Plausible |
| Glycine supplementation halts cancer progression | Pre-clinical animal models | Source unverified in live search for human RCTs. While animal models show suppressed tumor growth via metabolic trapping, translation to human oncology is clinically undocumented. | Level D | Translational Gap |
To translate these findings into a pragmatic longevity and health framework, we must separate healthy baseline metabolism from active tumor biology. Full Phase III RCT data is required before any of these interventions cross into standardized oncology.
High Confidence Tier (General Health & Longevity)
Experimental Tier (Active Malignancy)
Red Flag Zone (Avert)
One-Carbon Metabolism & The Folate Cycle
Serine is the primary carbon donor for the cellular folate cycle. The enzyme Serine Hydroxymethyltransferase (SHMT)—specifically SHMT1 in the cytosol and SHMT2 in the mitochondria—transfers a carbon atom from serine to tetrahydrofolate (THF). This reaction yields glycine and 5,10-methylene-THF. This newly minted one-carbon unit (5,10-methylene-THF) is then heavily utilized in the biosynthesis of purines and pyrimidines (thymidylate), which are the fundamental nucleic acids required for DNA replication in highly proliferative cancer cells.
Metabolic Trapping (The “Double Agent” Reversal)
The SHMT enzymatic reaction exists in a state of equilibrium and is entirely reversible based on mass action. In a controlled microenvironment where tumors are flooded with exogenous glycine (a high-glycine/low-serine ratio), the mass action ratio forces the SHMT enzyme to operate in reverse, converting glycine back into serine.
Crucially, this reverse reaction consumes 5,10-methylene-THF (the 1C unit) instead of producing it. By acting as a massive 1C “sink,” the excess glycine depletes the intracellular pool of available one-carbon units. This triggers a cascading failure: nucleotide biosynthesis halts, replication stress compounds, the cancer cell cannot repair its genomic damage, and tumor proliferation collapses.
The De Novo Serine Synthesis Pathway (SSP) Escape Mechanism
It is important to acknowledge a vital knowledge gap regarding dietary restriction alone: many aggressive tumors bypass dietary serine deprivation by upregulating the endogenous Serine Synthesis Pathway (SSP). They divert the glycolytic intermediate 3-phosphoglycerate (3-PG) into endogenous serine production via the rate-limiting enzyme Phosphoglycerate Dehydrogenase (PHGDH). Consequently, targeting cancer metabolism often requires a combinatorial approach: restricting exogenous intake while simultaneously utilizing pharmacological inhibitors of PHGDH to block the tumor’s internal synthesis escape route.
For liver cancer (HCC) Cyproheptadine (a 1st-Gen H1-antihistamine) also provides cancer protection. Like Desloratadine it results in weight gain, which is considered a plus for cancer patients that tend to lose weight due to loss of appetite.
Cyproheptadine is OTC in most countries outside the USA, and I ordered some, just in case, from India.
Looks like Desloratadine is prescription only in USA, but is OTC in other counties. Not sure if it is available in India.
I don’t see how you go serine free. Your body can make it from glucose or glycine. All protein has got it, even vegetable protein. You pretty much have to be keto, meaning almost all fat, no sugar or starch, almost no protein. It may stop the cancer, but not a long term solution for any living thing.
Yes - its a specially formulated medical diet (not something you can easily choose in a grocery store):
In clinical trials and pre-clinical models, a -SG diet is achieved exclusively through elemental or synthetic medical diets Dietary Manipulation of Amino Acids for Cancer Therapy, 2023.
This involves stripping all natural, intact protein from the diet. Instead, patients consume a proprietary, lab-formulated powder containing the other 18 amino acids, strictly calibrated to contain zero serine and zero glycine. Biotech companies pioneering this space engineer highly processed, precision meals to make these synthetic amino acid profiles palatable and compliant for human oncology patients.
A patient enrolled in a -SG clinical trial consumes a heavily calculated, synthetic diet. A daily meal plan relies on zero-protein carbohydrate and fat sources acting as delivery vehicles for the synthetic amino acid blend.
AlphaFold is an AI system developed by Google DeepMind that predicts a protein’s 3D structure from its amino acid sequence. It effectively solved a 50-year-old “grand challenge” in biology by achieving accuracy competitive with expensive, year-long experimental methods.
Key Versions & Milestones
How to Access It
Real-World Impact
AlphaFold is used by over 3 million researchers worldwide to accelerate work in:
[image]Google DeepMind +2
This story from the Australian has created a stir on twitter today. It reminded me of the Joan Manick video where she mentions discovering a cure for a type of lymphoma. She describes the results of Everolimus and another molecule and then mentions that Everolimus was going off patent. I wonder how many lives might be saved if certain treatments could be made profitable
The provided transcript details a presentation by Dr. Joan Mannick regarding Tornado Therapeutics’ development of next-generation rapalogs (mTOR inhibitors). The core thesis posits that while first-generation rapalogs (e.g., rapamycin, everolimus) are the most robustly validated pharmacological interventions for lifespan extension in model organisms, their clinical utility in geroscience is severely limited by an expiration of intellectual property and dose-limiting metabolic and hematologic toxicities.
The speaker attributes these side effects—specifically hyperlipidemia, hyperglycemia, and thrombocytopenia—to the “off-target” inhibition of the mTOR Complex 2 (TORC2). First-generation rapalogs potently inhibit mTOR Complex 1 (TORC1), which drives the longevity phenotype, but they also induce partial TORC2 inhibition under chronic dosing. Tornado Therapeutics asserts they have acquired an orphaned portfolio of highly selective, patent-protected TORC1 inhibitors from Novartis.
The company’s lead candidate, TOR101, demonstrates preclinical superiority by achieving sub-nanomolar TORC1 inhibition with zero detectable TORC2 inhibition up to 300 nM. Preliminary toxicology in rats and non-human primates suggests this selectivity effectively bypasses the lipid and platelet abnormalities endemic to everolimus. To de-risk clinical development, Tornado is targeting two indications with established precedent: oncology (Diffuse Large B-Cell Lymphoma, paired with R-CHOP) and immunosenescence (specifically, augmenting interferon-driven antiviral immunity against respiratory pathogens in the elderly).
While the pharmacological rationale for highly selective TORC1 inhibitors is biologically sound, the presentation functions primarily as an investor pitch. It selectively highlights small, successful trials (e.g., a 35-patient nursing home COVID-19 study) while conspicuously omitting the historical failures of similar compounds (like RTB101) in large-scale Phase 3 trials for respiratory tract infections. The pursuit of TORC1 selectivity is the correct evolutionary step for gerotherapeutics, but the translational gap between rodent toxicology and human geriatric efficacy remains formidable.
| Claim from Video | Speaker’s Evidence | Scientific Reality (Current Data) | Evidence Grade | Verdict |
|---|---|---|---|---|
| Aging causes mTOR to ignore fasting signals. | Sabatini Lab (Nature). | Verified. Pusapati et al., 2020 and others demonstrate age-related loss of nutrient-sensing fidelity in mTORC1 signaling. | Level D (Pre-clinical) | Strong Support |
| TORC2 inhibition causes hyperlipidemia, hyperglycemia, and shortens lifespan. | Lamming et al. studies. | Verified. Lamming et al., 2012 definitively proved chronic rapamycin induces hepatic insulin resistance via TORC2 disruption. | Level D (Pre-clinical) | Strong Support |
| Everolimus + R-CHOP yields ~100% OS in DLBCL. | Mayo Clinic data. | Contextualized. A Phase 1/2 trial by Witzig et al. (2018) showed an impressive 96% overall survival at 24 months, but in a highly selected, small patient cohort (n=24). | Level C | Plausible (Needs Phase 3) |
| mTOR inhibitors completely prevented severe COVID-19 in a nursing home trial. | Internal 35-person trial data (18 treated, 17 placebo). | Highly Debated. While the specific small trial may have shown these results, the speaker’s previous mTOR inhibitor (RTB101) failed a massive Phase 3 trial for respiratory illness prevention in the elderly, leading to company dissolution. | Level B/C (Conflicting) | Speculative (Survivorship Bias) |
| TOR101 causes zero toxicity up to 250 mg/kg. | 14-day rat/NHP tox studies. | Translational Gap. 14-day GLP tox is insufficient to declare chronic safety in humans. Toxicity often manifests during 28-day or 90-day chronic dosing. | Level D (Pre-clinical) | Speculative |
High Confidence Tier
Experimental Tier
Red Flag Zone
mTORC1 (Mechanistic Target of Rapamycin Complex 1)
mTORC1 is a serine/threonine kinase complex defined by its association with the scaffolding protein Raptor. It acts as the master regulator of cellular metabolism, integrating signals from insulin, growth factors, amino acids (specifically leucine and arginine), and cellular energy status (AMPK). When activated, TORC1 phosphorylates S6K1 and 4E-BP1, driving mRNA translation, ribosome biogenesis, and lipid synthesis, while concurrently inhibiting ULK1 to shut down macroautophagy. Selective inhibition of TORC1 is the ultimate target of longevity therapeutics, as it initiates cellular cleanup without disrupting basal metabolic homeostasis.
mTORC2 (Mechanistic Target of Rapamycin Complex 2)
mTORC2 is defined by its association with the protein Rictor. Unlike TORC1, TORC2 is relatively insensitive to nutrient availability and primarily responds to growth factor signaling (like insulin via PI3K). Its primary downstream target is the activation of Akt (Protein Kinase B) at Serine 473. Akt activation is essential for insulin signaling, glucose uptake, and cell survival.
The Pharmacodynamics of Rapalogs
Rapamycin does not inhibit the active kinase site of mTOR directly. Instead, it operates allosterically. It enters the cell and binds to the immunophilin FKBP12. This Rapamycin-FKBP12 complex then physically binds to the FRB domain of mTOR.
The summary skipped over the part I found interesting. The two drug combination boosted survival to 100%. Joan then mentions that Everolimus is going off patent so the search is on for a patentable rapalogue. The cost of a clinical trial is astronomical, so many known cures like this are not followed up.
This is a place where billionaires and philanthropists could make a huge difference, if they had the will.
It’s definitely a problem that once something is off-patent and/or no longer exclusive, it becomes essentially worthless to investigate it further.
Interesting news item from November of last year:
Old laboratory mice develop substantially fewer and less-aggressive lung tumors than younger animals in a new study led by Stanford University researchers. The discovery flies in the face of established dogma that holds that cancer risk increases with age, but it dovetails with what’s seen in very elderly people, in whom cancer risk appears to either level off or even decline with age.
However, maybe very old mice die from other kinds of cancer at a faster rate. So, depending on the age of the mouse, different types of interventions might be needed to reduce the chance they get cancer – one intervention might work best when the mouse is middle-age, but utterly fail to prevent cancer in old age.
Discovery and characterization of antitumor gut microbiota from amphibians and reptiles: Ewingella americana as a novel therapeutic agent with dual cytotoxic and immunomodulatory properties
“E. americana , isolated from the Japanese tree frog Dryophytes japonicus , achieved exceptional therapeutic outcomes including complete tumor remission (CR) due to its robust and sustained anticancer efficacy.”
“The successful identification of E. americana as a potent, naturally occurring anticancer agent establishes a proof-of-concept for microbiome-derived bacterial therapeutics and provides a foundation for the development of a new class of cancer treatments. These discoveries may ultimately lead to transformative advances in precision oncology and offer new hope for patients with treatment-refractory cancers. Future research directions should focus on expanding bacterial discovery programs, optimizing therapeutic protocols, investigating combination therapies, and advancing promising candidates toward clinical translation to fully realize the therapeutic potential of microbiome-derived cancer therapeutics.”
https://www.tandfonline.com/doi/full/10.1080/19490976.2025.2599562#d1e414
I’d love to hear from the hivemind on my pancreas!
I had a Simon One MRI 1/25 and they found a 4mm cyst/nodule on my pancreas. Nothing suspicious about it. They just said get a ct scan in a year.
My doc felt another MRI would be fine because he is only looking for changes. My rationale for this was the MRI is a fraction of the cost (sad to say!) and can catch other things with zero radiation.
I had my follow up MRI with Prenuvo 3/26 and they said it’s now 8mm.
My doc is not worried in the least. I’m not too worried either, but I also know there are not many second changes to catch P cancer early, so I’m here to double check.
The person at Prenuvo said they would recommend a focused MRI on my pancreas simply due to the fact it doubled in size in a year, but not because it looks suspicious.
I also assume this is a CYA for them and it might cost me thousands for no reason. If it’s something I should do, of course I will!
Hello Tananth, Desloratadine is available in India. I bought some. Thanks. Cheers
Benign growths are benign - yes. Have you had a suggestion to consult with an oncologist, or has your doc suggested a biopsy? Obviously nobody wants to go on fishing expeditions. It can be a personal decision. Nonetheless it is well worth keeping an eye on the situation with frequent imaging.
Thanks!
No one has suggested an oncologist or a biopsy. At most, it would be a focused mri or ct scan to take a closer look. He doesn’t feel I need it, and he is most likely correct…
Having said that, my friend was telling him about stomach pain for months and it turned out to be stage 4 pancreatic cancer, so I’m a little edgy and just trying not to soley rely on one person’s advice… as smart as he is
AI Detects “Invisible” Signs of Pancreatic Cancer Years Before Diagnosis
Thanks Cronos! I sent this to my doc to see if he can arrange for AI to read my images… I’m not expecting anything, but can’t hurt to ask!
