SCLC tumours replicated in mice from patients' CTCs

By Lynda Williams, Senior medwireNews Reporter

Scientists have used circulating tumour cells (CTCs) taken from patients with small-cell lung cancer (SCLC) to grow explant tumours (CDXs) in mice that retain the original’s morphological and genetic characteristics.

“CDXs also faithfully recapitulate responses of donor patients to platinum and etoposide, the standard-of-care chemotherapy for SCLC, enabling clinically relevant studies of SCLC biology and a readily generated and sustainable patient-derived model to test targeted therapeutics”, report Caroline Dive, from Cancer Research UK Manchester Institute, and co-authors.

Blood samples from six patients with chemotherapy-naïve, extensive-stage SCLC were enriched for CTCs. Three patients had tumours subsequently found to be sensitive to chemotherapy, while three patients had refractory tumours with disease progression within 3 months of chemotherapy.

The researchers injected CTC-enriched blood samples into the flanks of immunocompromised mice, and mice with CTCs from four of the patients had palpable tumours within 4 months.

As reported in Nature Medicine, diagnostic specimens and CDXs showed typical SCLC morphology and SCLC micrometastases were detected in the lungs and brain of a mouse carrying one of the CDXs.

When three CDXs were treated with cisplatin and etoposide, one had a significantly greater response to treatment than the others, one had an intermediate response and the last CDX did not respond.

The CDX responses to treatment mirrored the response of the patients’ tumours to chemotherapy, with patients surviving for 9.7, 3.5 and 0.9 months, respectively.

And genetic analysis confirmed that the CDX profiles matched the original tumour profiles, although there were differences in CDX samples taken from the left and right flanks of one mouse suggesting “tumour evolution”, the researchers say.

They cite the possibility of comparing CDX profiles produced from patient blood samples taken before chemotherapy and after drug-resistant relapse.

“[T]hese unique CDX models, generated from sequentially available, minimally invasive clinical samples now provide an unprecedented opportunity to study SCLC biology from diagnosis through treatment to progression”, Dive et al write.

“CDX models will also facilitate the search for new druggable targets in SCLC and enable routine in vivo testing of targeted therapies for a disease with clear unmet medical need.”

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