Beyond PSMA: Emerging Radioligand Therapy Targets in Solid Tumors

Updated July 2026. We revise this landscape each major conference season (SNMMI, ESMO, ASCO).

Radioligand therapy has two validated franchises: SSTR2 (somatostatin receptor 2) for neuroendocrine tumors, and PSMA for prostate cancer. Both are clinically proven, both are commercially crowded, and both have made one thing obvious to the entire field — the scarce resource in radioligand therapy is the next target.

The stakes are visible in the deal flow. The industry's biggest recent bets — RayzeBio's ~$4.1B acquisition, Fusion Pharmaceuticals' ~$2.4B, Point Biopharma — were, underneath the biology, races to own the right target before someone else did. There were more than 400 registered RLT trials as of mid-2025, and a growing share of them are aimed at targets beyond PSMA and SSTR2.

This is a working map of where that energy is going. For each target we note the lead indication and why it's attractive for radioligand therapy — assessed against the six criteria that make a good RLT target. None of these has an approved radioligand yet; most sit in early-to-mid-phase development, which is exactly what makes them interesting.

A landscape, not investment advice. Development stages move quickly and vary by program. Treat this as a starting map for triage, then verify current trial status and expression data for any target before acting. Every Nuclens target profile links back to its primary public sources.

Why the field is racing past PSMA and SSTR2

PSMA and SSTR2 worked because they clear the hard constraints cleanly: both are cell-surface, both internalize, both are highly expressed in their tumor with a workable normal-tissue profile, and both had ligand chemistry ready to adapt. That's the template every emerging target is measured against.

The problem with success is competition. Once a target is validated, programs pile in, and differentiation gets harder and more expensive. So the strategic frontier has moved to targets that clear the same scientific bar while the space is still relatively open — in new indications (small-cell lung, urothelial, pancreatic, lymphoma) and with next-generation isotopes like the alpha emitter ²²⁵Ac and the Auger/beta emitter ¹⁶¹Tb.

Here are the targets drawing the most attention.

DLL3 — small-cell lung cancer

Delta-like ligand 3 is one of the most-watched emerging targets, and for a specific reason: it is highly expressed on small-cell lung cancer (SCLC) and other neuroendocrine carcinomas, but minimal on normal adult tissue — an unusually clean tumor-versus-normal contrast. SCLC is aggressive and underserved, which raises the value of any credible new modality. DLL3 is also being pursued hard through other modalities (T-cell engagers, ADCs), which validates the biology even as radioligand programs advance.

Profile: DLL3

FAP — pan-tumor stroma

Fibroblast activation protein is different from the others here: it's expressed not on the cancer cells but on cancer-associated fibroblasts in the tumor stroma, across a very broad range of solid tumors. That pan-tumor reach is the appeal — one target, many indications — and FAP-targeted radioligands have generated substantial imaging and early therapeutic interest.

It's also a useful cautionary example for the framework: stromal expression means you have to think carefully about tumor-cell versus stromal delivery, and FAP appears in some normal tissues, so the normal-tissue/safety criterion needs real scrutiny rather than assumption.

Profile: FAP

GRPR — prostate and breast cancer

Gastrin-releasing peptide receptor is a GPCR overexpressed in prostate and breast cancer, and it's attractive as a peptide-receptor target — the same class as SSTR2, with well-behaved peptide ligand chemistry (antagonists such as RM2 and related scaffolds). GRPR is being explored both as a standalone target and as a complement to PSMA in prostate cancer, where PSMA-low disease is an emerging problem and a second handle is valuable.

Profile: GRPR

Nectin-4 — urothelial and triple-negative breast cancer

Nectin-4 is already clinically validated as a cancer target through the approved ADC enfortumab vedotin in urothelial carcinoma — meaning the biology, expression, and tolerability are unusually well characterized for an "emerging" radioligand target. That existing precedent de-risks the clinical-maturity criterion considerably. Radioligand and next-generation programs against Nectin-4 are advancing in urothelial and triple-negative breast cancer.

Profile: Nectin-4

CXCR4 — lymphoma and beyond

CXCR4 is a chemokine receptor overexpressed across many hematologic and solid malignancies. It stands out because its theranostic pair — pentixafor (imaging) and pentixather (therapy) — is among the more clinically advanced non-PSMA/non-SSTR radioligand efforts, with meaningful data in lymphoma and multiple myeloma. The imaging-first, therapy-follows pattern (the theranostic model that defined PSMA) is well established here.

Profile: CXCR4

STEAP1 / STEAP2 — prostate cancer

The STEAP family (six-transmembrane epithelial antigen of the prostate) is a leading candidate in the "beyond PSMA in prostate cancer" conversation, alongside DLL3 and CD46. STEAP1 in particular is a multi-pass transmembrane protein overexpressed in prostate cancer and is being pursued through several modalities, which is driving parallel interest in radioligand approaches — again, especially valuable as a second target for PSMA-low or PSMA-resistant disease.

Profile: STEAP1

How to evaluate the next one yourself

This list is a snapshot; the frontier keeps moving. The durable skill isn't memorizing which targets are hot this quarter — it's being able to evaluate any candidate quickly against the constraints that decide whether it can become a radioligand: cell-surface access, normal-tissue safety, tumor specificity and positivity, internalization, clinical precedent, and how crowded the space already is.

That's what Nuclens does. Describe the biology, indication, and modality you care about in plain English, and get a ranked, fully-sourced shortlist scored on exactly those dimensions — across a catalog of roughly 15,000 oncology targets, not a hand-picked list of the usual six.

Find your next target — free →

Nuclens is a first-pass target-triage platform for radioligand therapy. Development stages and trial statuses change; verify current data before making decisions. It does not replace experimental validation, clinical dosimetry, or regulatory assessment.