Joseph Bauer has been attaching nitric oxide to vitamin B12 and watching tumors shrink in laboratory animals since the second Bush administration. In 2007 it was mouse xenografts regressing under a B12 compound he liked to describe as a Trojan horse. In 2009 a Cleveland Clinic press release introduced the world to his “miracle dogs.” This June the same compound surfaced again, now aimed at glioblastoma, under a ScienceDaily headline promising a “new vitamin B12 therapy” against “deadly brain cancer.” The word carrying the most weight in that sentence, as it has for twenty years, is new.

The compound is nitrosylcobalamin, NO-Cbl for short: an ordinary B12 molecule with a nitric-oxide group bolted on. The idea is genuinely clever, worth saying plainly before the skepticism starts. Fast-growing tumors are hungry for B12 and tend to overexpress CD320, the receptor that imports it, so a vitamin freighted with a toxic gas can ride that receptor into cancer cells while mostly sparing tissue that isn’t reaching for B12 as fast. Conventional chemotherapy doesn’t aim like that; it’s limited by how much healthy fast-dividing tissue it poisons on the way to the tumor. If you’re inclined to root for a vitamin turned into a guided missile over carpet-bombing the patient, this is an easy story to want to believe.

Which is why it pays to read the study itself rather than the headline written about it. Published April 2 in Oncoscience by Bauer, Annette Sysel, and Michael Dunphy, it ran NO-Cbl through the NCI-60 panel of human cancer cell lines, tracked where the drug went in rats carrying glioblastoma tumors, and tested it alongside two other agents, TRAIL and the standard brain-cancer chemo temozolomide, in dishes of cultured U87 and D54 tumor cells. The rats carried the central result: after a systemic dose, NO-Cbl crossed the blood-brain barrier and built up in tumor tissue, where nitrate levels stayed elevated for at least 24 hours while normal brain cleared the drug faster. The authors are careful, in the paper if not in the press cycle, to call this what it is, a “pilot translational study.”

Here is what that pilot did not include. The compound reached the tumor. It did not shrink one. The rat experiment measured biodistribution, where the drug travels and how long it lingers, not survival, not tumor volume, not whether a single animal lived a day longer. The synergy that powered the “shows promise” coverage, the part where NO-Cbl plus temozolomide beat either drug alone, happened in plastic. Cells on a plate are not a brain, and a drug pooling in tumor tissue is a delivery result, not a treatment result. The press release accompanying the paper lists the next steps without flinching: “orthotopic validation, dose optimization, longitudinal nitric oxide tracking, and further mechanistic studies.” That is the to-do list of a project still working out, after two decades, whether the thing kills tumors in a living animal, never mind a person.

Line the studies up and the shape is hard to miss. Mice in 2007, dogs in 2009, rats in 2026, a press release at every stop. What has never appeared in twenty years of this work is a registered human trial. The cast of animals keeps escalating; the patient never arrives.

It is worth knowing who is making the case. Bauer and Sysel are named inventors on the patents covering NO-Cbl, including U.S. Patent 5,936,082 and 6,752,986, a detail the paper discloses to its credit. Bauer’s listed affiliation is not only the Cleveland Clinic but Nitric Oxide Services, LLC, the company positioned to commercialize the compound if it ever clears the animal stage. None of that makes the chemistry wrong. It does mean the man telling you a vitamin B12 derivative shows promise against brain cancer is the man who profits if you believe him, and the paper names no outside funding to set against that interest.

Then there is where it ran. Oncoscience comes from Impact Journals, the same house behind Oncotarget, which Clarivate stripped from its Journal Citation Reports in 2018 and which the National Library of Medicine dropped from new MEDLINE indexing in 2017, before MEDLINE re-accepted it in 2022. A venue is not an argument, and good work does turn up in unfashionable journals. But that history isn’t proof the finding is weak so much as a reason to keep your tolerance for press-release inflation low.

Glioblastoma is what makes this both worth chasing and easy to oversell. It is among the most lethal cancers in medicine, and it has buried a longer line of “promising” preclinical compounds than almost any disease, agents that dissolved tumors in mice and did nothing for the patients who came after. Temozolomide, the drug NO-Cbl was paired with in those dishes, is the rare survivor of that graveyard, and even so the regimen pairing it with radiation lifts median survival to just 14.6 months, against 12.1 months for radiation alone. A compound that wants a seat at that table has to clear a bar that biodistribution in a rat does not come close to touching.

So believe the chemistry, within its limits. NO-Cbl finds brain tumors, and that isn’t nothing. After twenty years, three species, and a patent portfolio, what Joseph Bauer reliably produces is a compound that locates cancer and a press release that locates reporters. The human trial is the one experiment he has never run.

Sources

  1. Oncoscience – Bauer, Sysel, Dunphy, “Selective blood–brain barrier penetration and tumor targeting of nitrosylcobalamin in glioblastoma” (2026)
  2. ScienceDaily – “New vitamin B12 therapy shows promise against deadly brain cancer” (2026)
  3. EurekAlert – “Vitamin B12-based therapy shows tumor-targeting potential against glioblastoma,” press release (2026)
  4. ScienceDaily – “Cancer Breakthrough: Tales Of ‘Trojan Horse Drug’ And ‘Miracle Dogs’” (2009)
  5. PLOS One – Bauer et al., NO-Cbl with mouse-xenograft tumor regression (2007)
  6. U.S. Patent 5,936,082 – “Metallocorrinoids as biologically compatible carriers of pharmacological agents” (Bauer, Sysel)
  7. International Journal of Molecular Sciences – “CD320 Receptor and Vitamin B12 as Potential Targets for Anti-Cancer Therapy” (2025)
  8. NEJM – Stupp et al., “Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma” (2005)
  9. The Scientist – “Oncotarget Journal Cut from Medline,” on Impact Journals’ indexing history (2018)
  10. Oncotarget – indexing timeline, including 2022 MEDLINE reinstatement