NPY receptors 1 and 2 overexpressed in breast and prostate cancer could enable targeted drug delivery and diagnostics | Research

The takeaway

Comprehensive review maps NPY receptor subtype expression across cancers, finding breast cancer has significant tumor-normal differences, with NPY analog modifications (stapling, conjugation) improving stability for targeted cancer therapy and diagnostics.

Breast cancer: best NPY target
Among all cancers, breast tissue shows the most significant NPY receptor overexpression difference between tumor and normal—enabling selective targeting with NPY analogs

What the researchers found

NPY R1 and R2: overexpressed in multiple cancers. Breast cancer: significant tumor-normal difference (most promising target). Key NPY binding residues identified. Stability solutions: sequence mods, stapling, conjugation. Best use: combinatorial with chemotherapy for targeted delivery.

Why it matters

Cancer drug delivery remains a major challenge. NPY receptors on tumor cells could serve as "addresses" for targeted drug delivery, reducing side effects while increasing tumor drug concentrations.

How the study worked

Comprehensive narrative review of NPY receptor expression in cancers, NPY analog structure-activity, and therapeutic strategies.

What this study cannot tell us

Review format. Most NPY targeting data is preclinical. Breast cancer is most promising but clinical trials are lacking. NPY analog stability in vivo remains challenging.

How to read the evidence

Comprehensive review mapping the field. Preclinical evidence with drug design guidelines.

When this study was published

Published in 2025.

The bigger picture

NPY receptor-targeted drug delivery joins a growing arsenal of peptide-guided cancer therapy approaches. The detailed receptor mapping and analog design guidelines provide a roadmap for clinical development.

Questions still open

Could NPY-targeted antibody-drug conjugates compete with existing cancer therapies?
Would NPY receptor PET imaging improve cancer staging?
Is Y1 or Y2 the better therapeutic target?

Common questions

Can NPY be used to target cancer?

Yes—NPY receptors are overexpressed on many cancer cells, especially breast and prostate cancer. By attaching cancer drugs to NPY analogs (modified versions of the peptide), drugs can be delivered specifically to tumors while sparing normal tissue. Breast cancer shows the most promising target profile.

How is NPY made stable enough for drug use?

Natural NPY breaks down quickly in the body. This review describes solutions: modifying the peptide sequence to resist enzymes, "stapling" the peptide to lock its shape, and conjugating it to drug delivery systems. These approaches improve stability while maintaining cancer cell targeting ability.

Read the original research

Neuropeptide Y receptors 1 and 2 as molecular targets in prostate and breast cancer therapy.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 187, 118117

View on PubMed ↗Publisher’s paper ↗

Citation

Tomić, Katarina; Kostevšek, Nina; Romeo, Sergio; Bassanini, Ivan. (2025). Neuropeptide Y receptors 1 and 2 as molecular targets in prostate and breast cancer therapy.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 187, 118117. https://doi.org/10.1016/j.biopha.2025.118117