What is the cancer signal, good or bad?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01InsulinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 29,691 people given it.4 reported

   12,537 people given it1 trial

   • Giving long-acting insulin early did not protect the heart, and it did not cause cancer either. 12,537 people with heart risk factors and blood sugar problems got insulin glargine or usual care, then were followed for about six years. Heart outcomes came out the same. Blood sugar dropping dangerously low was about three times more common on insulin. People on insulin gained about 1.6 kg while the others lost half a kilo. Sanofi, which sells the insulin, paid for it.

     The numbers ORIGIN: 12,537 people with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance or type 2 diabetes randomised to insulin glargine or standard care, median 6.2 years. Cardiovascular outcomes were neutral (hazard ratio 1.02, 95 percent confidence interval 0.94 to 1.11). Severe hypoglycaemia was 1.00 versus 0.31 per 100 person-years, and median weight rose 1.6 kg on insulin while falling 0.5 kg on standard care. No excess cancer (hazard ratio 1.00). Funded by Sanofi.

     New England Journal of Medicine, 2012· 12,537 people

2. 02Angiotensin-(1-7)PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 76 people given it.3 reported

   38 people given it2 trials

   • Given alone to people with an advanced cancer, it did not change the course of the disease. 20 people with sarcoma that had spread got a daily shot under the skin. Their cancer held off for about 2.7 months on average and they lived about 10.2 months. Two people with blood vessel tumours stayed stable far longer. A blood marker effect seen in the first study did not show up again. Everybody got the drug, so there is nothing to compare these figures against.

     The numbers 20 people with metastatic sarcoma received 20 mg subcutaneously daily. Median progression-free survival 2.7 months (95 percent confidence interval 1.4 to 4.1) and median overall survival 10.2 months (5.3 to 18.3). The placental growth factor biomarker effect seen in phase 1 was not confirmed. Two people with vascular sarcomas had prolonged disease stabilisation at 10 and 19 months.

     Sarcoma, 2016· 20 people

   • The first test in people was about safety, and it turned up serious harm at the top dose. 18 adults with advanced cancer got the peptide as a shot under the skin, daily for five days, with the dose raised group by group. At the highest dose one person had a severe stroke and another lost nerve function in the head, which recovered. One tumour shrank and three more stopped growing for over three months. These were very ill people and there was no comparison group.

     The numbers 18 adults with advanced solid tumours received escalating subcutaneous doses daily for 5 days on a 3 week cycle. Dose-limiting toxicities at 700 micrograms per kilogram were a grade 4 stroke and a grade 3 reversible cranial neuropathy. One patient had a 19 percent tumour reduction and 3 more had disease stabilisation beyond 3 months. Recommended phase 2 dose 400 micrograms per kilogram.

     Clinical Cancer Research, 2009· 18 peoplepoints the wrong way

3. 03IO102-IO103PeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 470 people given it.3 reported

   0 people given it1 trial

   • This trial was stopped because the vaccine did not do what it was meant to. Seventeen people with head and neck cancer had enrolled. The sponsor recorded the reason for stopping as the study failing to hit its target. A university hospital ran it, not the maker. No results have been published. The record shows a trial halted for lack of effect, which is a result in itself.

     The numbers Academic phase 2 in head and neck cancer, 17 enrolled, terminated. Reason recorded by the sponsor: unmet primary endpoint.

     ClinicalTrials.gov, Cliniques universitaires Saint-Luc, 2020· number of people not given

4. 04LanreotidePeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.4 reported

   0 people given it1 trial

   • Lanreotide slowed these tumours down, and that is a rare thing for a peptide to prove. 204 adults with advanced neuroendocrine tumours were split by chance. Half had a lanreotide shot every 28 days for up to two years. Half had a dummy shot, and nobody involved knew which. At two years, 65% of the lanreotide group were still free of tumour growth, against 33% on the dummy shot. People did not live longer and did not feel better. Ipsen, which sells the drug, paid for the trial.

     The numbers The CLARINET randomised phase 3 in metastatic enteropancreatic neuroendocrine tumours, showing prolonged progression-free survival on lanreotide. A hard clinical endpoint in a randomised trial, which very few peptides documented on this site can claim.

     New England Journal of Medicine, 2014· number of people not given

5. 05MecaserminPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 76 people given it.6 reported

   nobody was given it1 watch-only study

   • Men with naturally higher IGF-1 in their blood get prostate cancer somewhat more often. Nearly 200,000 men were followed for about seven years. 5,402 were diagnosed with prostate cancer and 295 died of it. The higher a man's level, the higher his risk, and a genetic analysis pointed the same way, which makes a real cause more likely. Nobody was given anything here. These were men with their own natural levels, not patients on mecasermin, and this does not show that treating a deficient child raises his cancer risk.

     The numbers The epidemiology that any page about giving people more IGF-1 has to state. 199,698 men in UK Biobank followed a mean of 6.9 years, 5,402 diagnosed with and 295 dying from prostate cancer. Higher circulating IGF-1 was associated with prostate cancer diagnosis (hazard ratio 1.09 per 5 nmol/L increment, 95 percent CI 1.05 to 1.12) and with prostate cancer mortality (1.15, 1.02 to 1.29), with hazard ratios corrected for regression dilution using repeat measurements. A two-sample Mendelian randomisation analysis using genetic instruments and outcome data from 79,148 cases and 61,106 controls supported a causal role (cis-MR odds ratio 1.34 per 5 nmol/L, 1.07 to 1.68). This is an association study in men with naturally varying IGF-1, not a study of mecasermin, and it does not establish that treating a deficient child raises cancer risk.

     International Journal of Cancer, 2021· 199,698 peopleobserved only, nobody was given it

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01SeleniumSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 35,533 people given it.1 reported

   35,533 people given it1 trial

   • Selenium did not prevent prostate cancer. A huge trial gave men selenium, vitamin E, both, or a dummy pill. None of it lowered prostate cancer. The claim that sold the bottles failed when it was tested at scale.

     The numbers SELECT. 35,533 men. Selenium, vitamin E, both, or placebo. No reduction in prostate cancer. The prevention claim that sold the bottles failed at scale.

     JAMA, 2009· 35,533 people

2. 02Vitamin DSupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 25,871 people given it.4 reported

   25,871 people given it1 trial

   • Vitamin D was tested properly, at scale, and it did not prevent cancer or heart disease. Nearly 26,000 adults were split by chance to take a daily vitamin D pill or a dummy pill. They were followed for more than five years. Neither of the two questions the trial was built to answer came out ahead. Most of these people already had decent vitamin D levels. Only about one in eight started out low. So this does not settle what happens when someone is truly short of it.

     The numbers VITAL. 25,871 participants randomised to 2,000 IU daily or placebo, median 5.3 years. Neither primary endpoint was met: no reduction in invasive cancer, no reduction in major cardiovascular events. Mean baseline 25-hydroxyvitamin D was 30.8 ng/mL and only 12.7% of participants were below 20.

     New England Journal of Medicine, 2019· 25,871 people

3. 03Green tea extractSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 1,075 people given it.4 reported

   1,075 people given it1 trial

   • A year of high dose green tea extract harmed the liver in a small but real share of women. 1,075 women past menopause took an extract with 843 mg of EGCG a day, or a dummy pill, for one year. Liver enzymes rose in 36 women on the extract against 4 on the dummy pill. Just over 1% had a liver problem serious enough to be recorded as such. Nausea and skin reactions were also more common on the extract. The National Cancer Institute paid for it.

     The numbers 1,075 postmenopausal women randomised to extract with 843 mg EGCG a day or placebo for one year. Adverse events 75.6 versus 72.8 percent; serious 2.2 versus 1.5 percent; more nausea and skin events on extract. ALT elevation in 36 (6.7 percent) versus 4 (0.7 percent), p < 0.001; 1.3 percent had ALT-related serious adverse events. US National Cancer Institute funded.

     Food and Chemical Toxicology, 2015· 1,075 people

4. 04EGCGSupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,172 people given it.5 reported

   1,075 people given it1 trial

   • Green tea extract damaged some livers, at ten times the dummy group's rate. 1,075 women past menopause took an extract delivering 843 mg of EGCG a day, or a dummy, for a year. A liver enzyme rose in 36 women on the extract, 6.7 percent, against 4 on the dummy, 0.7 percent. 1.3 percent had a liver problem recorded as serious. Overall side effect rates were close, 75.6 against 72.8 percent. Funded by the US National Cancer Institute.

     The numbers 1,075 postmenopausal women randomised to an extract delivering 843 mg EGCG a day or placebo for one year. Alanine aminotransferase elevation in 36 women on extract (6.7 percent) against 4 on placebo (0.7 percent), p < 0.001, with 1.3 percent having an ALT-related serious adverse event. Overall adverse event rates were similar, 75.6 against 72.8 percent, with more nausea and skin events on extract. US National Cancer Institute funded.

     Food and Chemical Toxicology, 2015· 1,075 people

5. 05SulforaphaneSupplementModerate. At least one finished study in people, and at least 100 people who took it. 7 completed trials, 423 people given it.6 reported

   170 people given it1 trial

   • Only the strongest dose did anything, and what it shifted was a chemical in urine. 170 adults in a polluted part of China were split by chance to a dummy drink or one of three strengths of broccoli sprout beverage, for 10 days. The top dose raised benzene clearance by 63.2 percent. The half dose and the fifth dose were no different from the dummy. The thing measured is a detoxification marker, not illness and not cancer. NIH funded.

     The numbers 170 adults randomised to placebo (n = 55) or one of three concentrations of broccoli sprout beverage for 10 consecutive days. Urinary benzene mercapturic acids rose significantly only in the high dose group, by 63.2 percent. The one half dose (+11.3 percent) and one fifth dose (-6.4 percent) were not significantly different from placebo. Median 24 hour urinary sulforaphane metabolite output was 24.6, 10.3 and 4.3 micromol across the three doses. The endpoint is a urinary detoxification biomarker, not a cancer rate. NIH funded, registered as NCT02656420.

     American Journal of Clinical Nutrition, 2019· 170 people

6. 06Zinc-L-carnosineSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

   0 people given it1 trial

   • Zinc-L-carnosine cut swallowing trouble in women having radiotherapy after breast cancer surgery. People were assigned to groups by chance, and the trial reported that the supplement prevented the painful swallowing radiation can cause. This is a very short report, and the journal record has no summary, so neither the number of people nor the size of the benefit can be checked here. It is one trial, in one hospital, in one narrow situation. Nothing here says the supplement helps anyone else.

     The numbers A randomised phase 3 trial in breast cancer patients receiving adjuvant radiotherapy, reporting prevention of dysphagia. A real randomised result with a symptom endpoint that matters to patients, in a specific population receiving a specific mucosal insult.

     The Breast Journal, 2020· number of people not given

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01AlbiglutideBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 10,304 people given it.

   9,463 people given it1 trial

   • Albiglutide cut heart attacks, strokes and cardiac deaths in people with diabetes and heart disease. Nearly ten thousand adults across 28 countries were split by chance between the drug and a dummy injection, and followed for about a year and a half. Nobody involved knew which. Seven in a hundred on the drug had a heart attack, stroke or cardiac death, against nine in a hundred on the dummy. Pancreas and thyroid problems were rare and evenly spread. GlaxoSmithKline funded it.

     The numbers 9,463 adults aged 40 and over with type 2 diabetes and cardiovascular disease, 610 sites, 28 countries, randomised 1:1 to albiglutide 30 to 50 mg weekly or placebo, median follow-up 1.6 years. Primary composite (cardiovascular death, myocardial infarction, stroke): 338 of 4,731 (7 percent) against 428 of 4,732 (9 percent), hazard ratio 0.78 (95 percent CI 0.68 to 0.90), superiority P equals 0.0006. Pancreatitis 10 against 7, pancreatic cancer 6 against 5, medullary thyroid carcinoma 0 against 0. Funded by GlaxoSmithKline.

     Lancet, 2018· 9,463 people

2. 02BPTESSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 513 people given it.1 reported

   513 people given it2 trials

   • The only proper test of blocking this enzyme in people found nothing. 444 adults with advanced kidney cancer got telaglenastat plus the cancer drug cabozantinib, or a dummy pill plus cabozantinib. Both groups went about 9.2 and 9.3 months before their cancer grew again. That is the same result twice. Telaglenastat is a different drug from BPTES, but it hits the same target, and this is cancer medicine, not ageing. The maker paid for the study.

     The numbers The only randomised human data on glutaminase inhibition. 444 patients with metastatic renal cell carcinoma. Median progression-free survival 9.2 months with telaglenastat plus cabozantinib versus 9.3 months with placebo plus cabozantinib, hazard ratio 0.94, P = 0.65. Manufacturer funded. Oncology, not senescence.

     JAMA Oncology, 2022· 444 people

   • A smaller study leaned toward the drug without settling anything. 69 adults with advanced kidney cancer got telaglenastat or a dummy pill, both along with the cancer drug everolimus. Two got the drug for every one on the dummy pill. Cancer took 3.8 months to grow again on the drug, against 1.9 months. The bar for success was set loose, so this would not count as proof elsewhere. Serious side effects hit 74 percent against 61 percent. The maker paid for it.

     The numbers 69 patients randomised 2:1. Median progression-free survival 3.8 months versus 1.9 months, hazard ratio 0.64, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. Grade 3 to 4 events in 74 percent versus 61 percent. Manufacturer funded.

     Clinical Cancer Research, 2022· 69 people

3. 03TelaglenastatSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 513 people given it.1 reported

   513 people given it2 trials1 found nothing

   • found nothingTelaglenastat was tested properly in a large study, and it did not work. 444 adults with advanced kidney cancer took telaglenastat or a dummy pill, both along with the cancer drug cabozantinib. The cancer grew again after 9.2 months on the drug and 9.3 months on the dummy pill. Tumours shrank in 31 percent against 28 percent, the same answer. Serious side effects were common in both groups, 71 percent against 79 percent. The maker paid for it.

     The numbers 444 patients randomised, double blind, placebo controlled. Median progression-free survival 9.2 versus 9.3 months, hazard ratio 0.94, 95 percent confidence interval 0.74 to 1.21, P = 0.65. Overall response 31 versus 28 percent. Grade 3 to 4 adverse events in 71 versus 79 percent. Manufacturer funded. The primary endpoint was missed.

     JAMA Oncology, 2022· 444 people

   • A second, smaller study hinted at a benefit and proved nothing. 69 adults with advanced kidney cancer, most already through three treatments, got telaglenastat or a dummy pill, both along with the cancer drug everolimus. Two got the drug for every one on the dummy pill. The cancer grew again after 3.8 months against 1.9 months. One tumour shrank. The study set itself a low bar and still did not clear it cleanly. Serious side effects hit 74 percent against 61 percent. The maker paid for it.

     The numbers 69 patients randomised 2:1 after a median of three prior lines. Median progression-free survival 3.8 versus 1.9 months, hazard ratio 0.64, 95 percent confidence interval 0.34 to 1.20, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. One partial response on telaglenastat. Grade 3 to 4 events 74 versus 61 percent. Manufacturer funded.

     Clinical Cancer Research, 2022· 69 people

4. 04TrametinibSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,192 people given it.

   322 people given it1 trial

   • In advanced melanoma with a BRAF mutation, trametinib on its own held the cancer back longer than chemotherapy and more people were alive at six months. Rash, diarrhoea and swelling were the common side effects. This is the trial that led to its approval as a single drug.

     The numbers 322 patients with metastatic melanoma carrying a BRAF V600E or V600K mutation randomised 2:1 to trametinib 2 mg daily or chemotherapy, open-label (METRIC). Median progression-free survival 4.8 versus 1.5 months (HR 0.45, 95% CI 0.33 to 0.63). Overall survival at 6 months 81% versus 67% despite crossover (HR 0.54). Rash, diarrhoea and peripheral oedema were most common; reductions in ejection fraction and eye effects were infrequent.

     The New England Journal of Medicine, 2012· 322 people

5. 05GDF15BiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 313 people given it.3 reported

   187 people given it1 trial

   • Blocking GDF15 put weight back on people with cancer who were wasting away. 187 patients with cancer wasting and high GDF15 were put into four groups. Three got the antibody at rising doses. One got a dummy shot. Shots came every four weeks, three times. By twelve weeks the drug groups had gained about 1.2 to 2.8 kilograms more than the dummy group. Appetite and daily activity got better at the top dose. Pfizer paid for the study.

     The numbers 187 patients with cancer cachexia and GDF15 of at least 1,500 pg/mL (40 percent non-small-cell lung, 32 percent pancreatic, 29 percent colorectal) randomised 1:1:1:1 to ponsegromab 100, 200 or 400 mg or placebo every 4 weeks for three doses. Median weight gain versus placebo at 12 weeks: 1.22 kg (95 percent credible interval 0.37 to 2.25), 1.92 kg (0.92 to 2.97) and 2.81 kg (1.55 to 4.08). Appetite, cachexia symptoms and physical activity improved at 400 mg. Adverse events in 70 percent on ponsegromab and 80 percent on placebo. Funded by Pfizer.

     New England Journal of Medicine, 2024· 187 people

   Also measured in animals or in the lab

   • In mice with tumours. An antibody that blocks GDF15's docking spot stopped the wasting. It showed GDF15 burns off fat and muscle through the nervous system, not only by killing appetite. This is the animal work behind blocking GDF15 in people.

     The numbers An antibody against GFRAL prevented cachexia in tumour-bearing mice, reversing excess lipid oxidation, and identified a sympathetic lipolytic axis by which GDF15 wastes fat and muscle independently of anorexia. The preclinical basis for blocking the pathway in people.

     Nature Medicine, 2020· animal study

6. 06EnobosarmSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 159 people given it.5 reported

   159 people given it1 trial1 found nothing

   • found nothingMuscle did grow, in people who were losing it to cancer. 159 patients who had already lost weight took one of two doses of enobosarm or a dummy pill for up to about four months. Muscle mass rose on both doses, by roughly 1 to 1.5 kg, while the dummy group did not change. Here is the limit. Growing muscle is not the same as being able to do more, and the larger studies that followed did not succeed.

     The numbers 159 patients with cancer and at least 2% weight loss, randomised to enobosarm 1 mg, 3 mg or placebo for up to 113 days. Total lean body mass rose significantly on both doses (median 1.5 kg on 1 mg, 1.0 kg on 3 mg) while placebo did not change. This is the Phase 2 trial that preceded the POWER Phase 3 program.

     The Lancet Oncology, 2013· 159 people

7. 07LandogrozumabBiologicModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 726 people given it.

   125 people given it1 trial

   • In people with pancreatic cancer, the antibody did not help and the treated groups did worse. 125 patients on chemotherapy were split by chance between two doses of the drug and a dummy injection. Those on the dummy lived about ten and a half months. On the lower dose it was just under ten months, and on the higher dose about eight. Tumour shrinkage and time before the cancer grew again also favoured the dummy. Wasting from cancer is not the wasting of old age.

     The numbers 125 participants with pancreatic cancer on chemotherapy, randomised to LY2495655 at 100 mg, 300 mg or placebo (NCT01505530, results posted 2018). Every measure favoured placebo. Median overall survival 10.45 months on placebo against 9.82 at 100 mg and 8.02 at 300 mg. Progression free survival 8.21 against 6.87 and 4.90 months. Response rate 26.8 percent against 25.6 and 22.0 percent. The treated arms did worse. Wasting from cancer is a different mechanism from disuse or ageing, and this is the population where the idea failed hardest.

     ClinicalTrials.gov, 2015· 125 people

8. 08NavitoclaxSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 137 people given it.2 reported

   46 people given it1 trial

   • Navitoclax on its own barely touched advanced ovarian cancer. 46 women whose cancer no longer responded to chemo took it, with no comparison group, after a median of four earlier treatments. One woman's tumour shrank. 15 saw theirs hold steady. Half were back to growing cancer within about seven weeks. In 12 of the 46, platelets dropped to dangerous levels, which forced a dose cut in 8 and stopped treatment in 3. The authors called the results poor.

     The numbers 46 women with platinum-resistant high-grade serous ovarian cancer, median four prior lines, single-arm. Three-month progression-free survival 22.7 percent, median progression-free survival 1.64 months, one partial response and 15 stable diseases. Grade 3 or 4 thrombocytopenia in 12 of 46, causing dose reduction in 8 and discontinuation in 3. The authors concluded activity was poor.

     Gynecologic Oncology, 2022· 46 people

9. 09MetforminSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 489 people given it.6 reported

   nobody was given it1 watch-only study

   • The longest follow-up in people we have found no drop in deaths. 3234 adults at high risk of diabetes were given metformin, an intensive lifestyle program, or a dummy pill. After a median 21 years, 453 had died. Neither metformin nor lifestyle cut deaths from any cause, cancer or heart disease. Preventing diabetes and preventing death were different questions, and only the first one moved.

     The numbers DPP and DPPOS. 3,234 adults at high risk for type 2 diabetes, median 21 years. 453 deaths. Neither metformin nor lifestyle reduced all-cause, cancer or cardiovascular mortality.

     Diabetes Care, 2021· 3,234 peopleobserved only, nobody was given it

10. 10RuxolitinibSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 309 people given it.

    nobody was given it1 watch-only study

    • Five years on, the same cancer trial still favours the drug. Spleen shrinkage lasted a median of just over three years. People started on ruxolitinib lived longer than those started on the dummy pill, even though most of the dummy group switched onto the drug part way through. Tiredness and diarrhoea were the common complaints. Low red cells and low platelets nearly all appeared in the first six months. Everyone here had the same bone marrow cancer, and nothing in it measures ageing.

      The numbers The five-year follow-up of the same myelofibrosis trial, reporting durability of spleen response and long-term safety in that population. Still a cancer population, still no ageing endpoint.

      Journal of Hematology and Oncology, 2017· number of people not givenobserved only, nobody was given it

Other compounds

1. 01GW0742Small moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, 1 lab study, no human study.3 reported

   2 animal or lab studies

   What people using it report

   • Concerns raised are borrowed from the related compound: skin changes, and unresolved arguments about rodent findings on heart size and on cancer. Nobody in these threads reports an adverse effect from this compound, because nobody in them reports taking it.

   Measured in animals or in the lab

   • In mice given a chemical that causes bowel cancer. GW0742 reduced the cancer, working in a different way from drugs that block the COX2 enzyme. This is mouse work, and it points against the family's cancer worry.

     The numbers Azoxymethane-induced colon cancer in wild-type and PPAR-beta/delta-null mice. GW0742 had inhibitory effects on colon carcinogenesis, acting through mechanisms independent of COX2 inhibition. Mouse work, and it points opposite to the class cancer fear.

     Carcinogenesis, 2008· animal study

   • found nothingIn a dish and in mice. Neither GW0742 nor GW501516 made five kinds of human cancer cells grow faster, and tissue from treated mice showed no change in these growth markers either. This argues against the idea that this drug family feeds tumours.

     The numbers GW0742 and GW501516 tested in five human cancer cell lines with and without serum. Neither increased cell growth, Akt phosphorylation, VEGF or COX2, and liver, colon and colon polyps from treated mice showed no change in these markers either. A published argument against the tumour-promotion hypothesis for this class.

     Carcinogenesis, 2007· lab (cells in a dish)

2. 02DT2216Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 20 people given it.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice and in a dish. DT2216 was gentler on platelets than navitoclax in a dish, and stronger against cancer cells that need BCL-xL. It slowed human tumours grown in mice without a big platelet drop. It was designed this way because platelets have little of the cell tool it uses.

     The numbers Human cell lines and mouse xenografts. DT2216 was less toxic to platelets than ABT-263 in vitro, more potent against BCL-xL-dependent cancer cells, and inhibited xenograft tumour growth in mice without appreciable thrombocytopenia. The design rationale is that VHL is poorly expressed in platelets.

     Nature Medicine, 2019· animal study

   • In mice and in a dish. DT2216 worked against a type of lymph cancer that needs BCL-xL. That adds to the lab case for destroying the protein instead of just blocking it.

     The numbers Cells and mice. Activity against BCL-xL-dependent T cell lymphoma models, extending the preclinical case for selective degradation over inhibition.

     Journal of Hematology and Oncology, 2020· animal study

3. 03OSKM Cyclic Partial ReprogrammingBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 6 animal studies, no human study.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, from the Yamada and Yamanaka labs. Switching the reprogramming genes on and then taking the doxycycline switch away caused tumours in several tissues. The tumour cells were unformed and abnormal, with big changes to the chemical tags across their DNA. The kidney tumours looked like Wilms tumour, a childhood cancer. Stem cells taken from those tumours grew into normal kidney cells, which proves the tumours came from the tags, not from damaged genes.

     The numbers Mouse, from the Yamada and Yamanaka laboratories. Transient expression of reprogramming factors followed by doxycycline withdrawal produced tumours in various tissues, consisting of undifferentiated dysplastic cells with global DNA methylation changes. Kidney tumours shared characteristics with Wilms tumour. Stem cells derived from those tumour cells gave rise to non-neoplastic kidney cells, proving the tumours were epigenetically rather than genetically driven.

     Cell, 2014· animal study

4. 04Alpha-2-MacroglobulinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 75 people given it.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • A comparison of naked mole rat blood with human blood. The naked mole rat, which lives a long time and rarely gets cancer, carried A2M at 8.3 milligrams per millilitre against 4.4 in human blood. It also had less total protein, more enzyme-blocking power, less enzyme activity and a different sugar coating that makes the protein heavier. The authors suggest this may help explain that animal's resistance to cancer and its long life. This is a comparison of two species' blood, not a treatment.

     The numbers Comparative analysis of naked mole rat and human plasma. Naked mole rat plasma carried A2M at 8.3 plus or minus 0.44 mg/mL versus 4.4 plus or minus 0.20 mg/mL in human plasma, with lower total plasma protein (38.7 versus 61.7 mg/mL), higher antitryptic activity, lower proteolytic activity, and a different predicted glycosylation giving a higher molecular weight. The authors suggest a possible contribution to that species' cancer resistance and longevity. This is comparative biochemistry, not an intervention.

     PLoS One, 2015· lab (cells in a dish)

5. 05ABT-737Small moleculePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Clearing worn-out cells, with genes or a clean-up drug, or removing a type of immune cell, shrank tumours and helped mice with a type of lung cancer live longer. Worn-out immune cells were also seen in human lung tissue before cancer, but that was only an observation, not a treatment.

     The numbers Mouse. Genetic or senolytic ablation of senescent cells, or macrophage depletion, reduced tumour burden and increased survival in KRAS-driven lung cancer models. Macrophages with senescent features were also found in human pre-malignant lung lesions, an observation rather than an intervention.

     Cancer Cell, 2023· animal study