Despite the poor prognosis of these lineage states, numerous therapeutic vulnerabilities exist with expression of cell surface targets identified with transcriptional profiling and single CTC phenotyping.

LumB CRPC detected by CTC RNAseq was also prognostic for resistance to 177Lu-PSMA-617 despite similar PSMA expression. Evidence of NEPC emergence as a resistance mechanism to 177Lu-PSMA-617 was also observed.

We confirmed the prognostic relevance of this signature using an independent tissue biopsy cohort, matching what was observed in the liquid biopsy cohort.

Overall survival of patients with these states was also markedly different, with LumB CRPC exhibiting a median OS of only 6 months that enriches for liver metastatic adenocarcinoma that is molecularly distinct from NEPC (median OS 3.7 mos).

We validated that these are epithelial cells with transcriptional analysis across these lineage states. Importantly, proliferation indices were quite different across NEPC and Luminal B-like lineage states in contrast to Luminal-A.

We then analyzed 237 samples from 117 patients with metastatic prostate cancer in a multi-center study to identify lineage states including NEPC, Luminal A like and Luminal B like states.
@danafarber.bsky.social @uwhealth.bsky.social @ucsdmedschool.bsky.social @fredhutch.bsky.social

We refined technology/assays published by @ascocancer.bsky.social @theaacr.bsky.social to achieve purity of CTCs equivalent or superior to tissue biopsies.

Deeply grateful for this collaborative team of dedicated researchers and scientists seeking to do better in our shared fight against cancer. New data and trials on the way! @theaacr.bsky.social @helloeacr.bsky.social #Langlab #Sharifilab #CirculatingBiomarkerCore