# Why anti-angiogenic therapy can fail

> A 13-cancer single-cell atlas points to tumor-educated pericytes as a possible source of escape routes, but the proposed dual-target strategy remains preclinical.

_Source: Peer-reviewed Science Bulletin study; independently checked against PubMed, Crossref, and OpenAlex records. · 2026-08-28 · 6 min read · Verified against primary sources_

Canonical: https://iyu.app/e/tumor-pericytes-antiangiogenic-resistance

## The 60-second version

Tumor-educated pericytes may provide an alternative blood-vessel growth route when VEGF-focused cancer therapy is blocked.

**Key points**

- The study built a pan-cancer atlas from 1.24 million cells across 13 cancer types.
- MCAM-positive immature pericytes were identified as a source of PGF and ANGPT2, signals linked to alternative angiogenesis.
- An MCAM-directed antibody-drug conjugate combined with VEGFR inhibition showed stronger tumor control in experimental systems.
- The result is preclinical and includes industry-affiliated authors; it does not establish human benefit or a clinical standard.

**Verdict.** The paper expands the resistance model from vessel-lining cells to the cells that support them, but the proposed treatment needs independent and clinical validation.

## Full explainer

The central finding is a mechanism, not a ready-made cancer treatment. By mapping **1.24 million cells across 13 cancer types**, the study identifies tumor-altered pericytes as a possible escape route when therapy focuses mainly on VEGF signaling.


### The finding — A second route around blocked vessels

Anti-angiogenic drugs try to starve tumors by disrupting the blood-vessel growth they need. The familiar target is the endothelial cell, the cell lining the vessel, and its VEGF signals. This paper argues that the surrounding support cells deserve equal attention.

- **1.24M** — individual cells analyzed
- **13** — cancer types in the atlas
- **2** — vessel-support factors highlighted: PGF and ANGPT2


### The mechanism — Tumors can educate their support cells

The researchers focused on MCAM-positive immature pericytes, or imPCs. These cells sit around vessels and, under altered Notch signaling and low-oxygen stress, were identified as a major source of PGF and ANGPT2. Those signals can support alternative angiogenesis, helping explain why a single VEGFR-focused approach may lose effectiveness.

> Resistance may be a network problem, not a one-molecule problem.


### The proposed fix — Target the lining and its support

In the reported experiments, an MCAM-directed antibody-drug conjugate was used to remove pro-angiogenic pericytes and was combined with VEGFR inhibition. The combination showed stronger anti-angiogenic effects and tumor control than the single-route strategy in experimental systems.

> **⚑ Caveat:** This is not evidence of a treatment that works in people. The atlas is mainly a map of molecular relationships, and the combination remains a translational proposal requiring independent preclinical and clinical testing. Several authors are affiliated with Multitude Therapeutics, which also warrants close conflict-of-interest review.


### What remains open — A promising map is not a prescription

- **What the paper supports:** Pericytes and PGF/ANGPT2 are plausible contributors to anti-angiogenic resistance across the analyzed cancers.
- **What it does not prove:** That MCAM targeting benefits patients, works in every tumor, or is safer or better than current care.
- **Next evidence needed:** Independent replication, well-defined experimental models, biomarker testing, and randomized clinical trials.

**So what should a reader do?** Treat this as a map of a possible resistance mechanism, not as a reason to change cancer care. The next decisive test is whether the dual strategy improves patient outcomes under controlled clinical conditions.


## Primary sources

- [Telegram post 1440](https://t.me/CNSmydream/1440)
- [Science Bulletin paper](https://doi.org/10.1016/j.scib.2026.06.022)
- [PubMed abstract (PMID 42342510)](https://pubmed.ncbi.nlm.nih.gov/42342510/)
- [Crossref metadata](https://api.crossref.org/works/10.1016%2Fj.scib.2026.06.022)
- [OpenAlex record](https://api.openalex.org/works/https://doi.org/10.1016/j.scib.2026.06.022)

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