Judah Folkman proposes tumor angiogenesis

Historical milestone — this page describes an event dated 1971. It is not current breaking news.

One paper, one idea

On 18 November 1971 the New England Journal of Medicine published a paper by the surgeon Judah Folkman, in volume 285, pages 1182 to 1186. Its title was "Tumor angiogenesis: therapeutic implications."

Angiogenesis means the growth of new blood vessels. The proposal in that title is the whole story: if tumors need new vessels, then blocking vessel growth is a way to treat them.

It took more than three decades for that sentence to become a drug.

Why a tumor needs its own plumbing

NCI describes the biology in current terms. To grow beyond a certain size, tumors need to form new blood vessels through angiogenesis. The tumor itself sends the signals that start the process.

Without a supply line, tissue cannot get oxygen or nutrients, and cannot clear waste. A tumor that cannot build vessels stays small.

NCI's account of what angiogenesis inhibitors do follows directly. They interfere with those signals to prevent a blood supply from forming. Where a tumor already has one, the drugs can cause its vessels to die, shrinking the tumor.

From idea to molecule

Folkman's laboratory spent decades looking for substances that block vessel growth naturally.

One result was published in the journal Cell in January 1997, by M. S. O'Reilly and colleagues including Folkman. They reported endostatin, described as an angiogenesis inhibitor produced by a tumor of blood vessel cells, and identified as a 20 kilodalton fragment of collagen XVIII.

The paper's claims were specific. Endostatin inhibited endothelial cell growth, blocked angiogenesis and tumor growth in mice, and regressed primary tumors to dormant microscopic lesions with no toxicity observed. The authors described the effect as dormancy therapy.

Endostatin itself did not become a widely used cancer drug. The strategy did.

The drug that actually arrived

Bevacizumab, sold as Avastin, works on the same principle from a different angle. Its label states the mechanism: it binds VEGF and prevents VEGF from interacting with its receptors, Flt-1 and KDR, on the surface of endothelial cells.

VEGF binding to those receptors is what drives endothelial cells to multiply and form new vessels. Remove the signal and the construction stops.

FDA records show Avastin's original approval on 26 February 2004, under application BLA 125085. That is 33 years after the 1971 paper.

Bevacizumab now appears across oncology. It turns up in colorectal cancer, added to a chemotherapy tablet in later lines, and in ovarian cancer, where it forms part of maintenance therapy after treatment. Our page on targeted therapy covers where these drugs fit.

What blocking blood vessels does and does not achieve

The honest summary is that angiogenesis inhibitors slow tumors more often than they eliminate them.

Tumors adapt. Blocking one vessel-growth signal leaves others, and cancers can route around a single blockade. That is the general pattern with targeted drugs, and it is why they are usually given alongside chemotherapy rather than instead of it.

There is a cost side too. Vessels matter for wound healing, blood pressure control and kidney function, so drugs that interfere with vessel growth have effects in all three places.

When to get checked

Angiogenesis is a mechanism, not a disease, so there is no symptom list attached to it. What matters is the cancers these drugs treat, and those are found the usual ways.

Screening carries the firm numbers. The US Preventive Services Task Force gives colorectal cancer screening a grade A for adults aged 50 to 75 and a grade B for adults aged 45 to 49. It gives biennial mammography a grade B for women aged 40 to 74. It gives annual low-dose CT lung screening a grade B for adults aged 50 to 80 with a 20 pack-year smoking history who smoke now or quit within 15 years.

Outside those programs, the prompts are symptoms that do not settle. Blood where there should not be blood, whether in stool, urine or when coughing. Unexplained weight loss. A lump that persists. Bloating that is new and daily rather than tied to meals. A cough or hoarseness past three weeks. Our page on cancer screening overview sets out which programs exist and who they are for.

What the wider numbers look like

The 2,114,850 new US cancer cases and 626,140 deaths expected in 2026 are American Cancer Society projections, reprinted by SEER. NCI's own SEER measurement of five-year relative survival across all sites, for cases from 2016 to 2022, is 70.5 percent. In the mid-1970s, around the time Folkman published, it was about 50 percent.

Angiogenesis inhibitors are one contributor among many to that shift, alongside screening, surgery, radiation, chemotherapy, targeted drugs and immunotherapy. No single line of research owns the change.

These figures cover every cancer type together. They describe a population and cannot describe an individual.

What this does not mean

A 1971 hypothesis is not a treatment. The gap between the idea and an approved drug was 33 years.

Early expectations that cutting off a blood supply would eliminate tumors were not met. In practice these drugs delay growth, and tumors often find ways around the blockade.

Endostatin's dramatic mouse results did not translate into a standard human therapy. That gap between animal and human results is ordinary in cancer research, not a scandal.

And whether an angiogenesis inhibitor belongs in any particular treatment plan depends on the cancer type, the stage and the person, decided with an oncologist.

Sources

• Folkman J, Tumor angiogenesis: therapeutic implications, New England Journal of Medicine 1971 (record via NCBI) — https://pubmed.ncbi.nlm.nih.gov/4938153/
• O'Reilly MS and others, Endostatin: an endogenous inhibitor of angiogenesis and tumor growth, Cell 1997 (record and abstract via NCBI) — https://pubmed.ncbi.nlm.nih.gov/9008168/
• NCI, Targeted Therapy for Cancer — https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
• FDA Drugs@FDA record for BLA 125085 (Avastin), original approval 26 February 2004, via the openFDA API — https://api.fda.gov/drug/drugsfda.json?search=application_number:%22BLA125085%22&limit=1
• FDA prescribing information for AVASTIN, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22AVASTIN%22&limit=1
• SEER Cancer Stat Facts, Cancer of Any Site — https://seer.cancer.gov/statfacts/html/all.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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