09/09/2026 - Press release
Biliary tract cancer comprises a group of rare and highly heterogeneous tumours that can originate in different parts of the biliary tree, the network of ducts that carries bile from the liver to the gallbladder and small intestine. These tumours have different molecular profiles depending on their location. In recent years, the outlook for people diagnosed with this type of tumour has changed with the introduction of immunotherapy as a first-line treatment, although the benefit remains modest. Approximately four in ten patients have molecular alterations that could make them eligible for existing targeted therapies. The challenge is now how to detect these mutations in order to select the most appropriate treatment.
International guidelines recommend that all patients with advanced biliary tract cancer undergo molecular profiling using genomic sequencing techniques, which can identify alterations that may be targeted with specific treatments. However, obtaining an adequate tissue sample is often difficult in these tumours because of their location in the bile ducts or liver. In many cases, the quantity or quality of the tissue is insufficient to complete the molecular analysis. In this context, a study led by researchers at the Hospital del Mar Research Institute (HMRIB) has shown that liquid biopsy, based on a simple blood sample, is a reliable alternative for the molecular profiling of these tumours, broadening patients' access to precision medicine.
Dr Laura Visa, a consultant in the Medical Oncology Department at Hospital del Mar and a researcher with the Gastroesophageal Carcinogenesis Research Group at HMRIB, explains that the findings support the conclusion that "liquid biopsy is a highly useful alternative when there is insufficient tumour tissue available to carry out a comprehensive molecular analysis. It enables us to identify actionable alterations and facilitate patients' access to targeted treatments." The study has been published in the journal Clinical Cancer Research.

From left to right: Beatriz Bellosillo, Laura Visa, Clara Montagut, Jordi Badia.
The largest cohort analysed to date
To carry out the study, the researchers analysed molecular data from 10,937 patients with biliary tract cancer. As Dr Clara Montagut, head of the Medical Oncology Section at Hospital del Mar and deputy director of HMRIB, explains, "one of the study's key strengths is that it includes the largest international cohort analysed to date, giving the findings considerable clinical validity. This was made possible through our collaboration with Guardant Health, a leading biotechnology company based in California." This analysis enabled the researchers to describe the molecular profile of biliary tract cancer and determine the frequency of the main mutations for which treatments are currently available.
The findings were confirmed by analysing a smaller cohort of 126 patients with metastatic or inoperable cholangiocarcinoma from nine centres across Spain. Genomic data from both tissue and blood samples were available for these patients, allowing the researchers to compare the results obtained using liquid biopsy with those obtained from tissue biopsy. The two techniques showed 83% concordance in the detection of the most clinically relevant molecular alterations. In addition, liquid biopsy results were available for 90% of patients, whereas tissue sequencing could only be carried out in half of them. This reinforces the potential of liquid biopsy to broaden patients' access to precision medicine. For these reasons, Dr Visa points out that liquid biopsy "is a reliable, accessible, rapid and minimally invasive alternative for the molecular profiling of patients with biliary tract cancer, thereby facilitating access to targeted therapies."
The study also shows that a higher circulating tumour DNA burden is associated with a poorer prognosis, suggesting that this technique could provide relevant prognostic information. Dr Beatriz Bellosillo, head of the Innovation and Precision Medicine Unit of the dibi network and of the Liquid Biopsy Unit at Hospital del Mar, explains that "both the tumour burden detected in the blood and the molecular heterogeneity of the tumour are associated with patient survival, suggesting their potential as prognostic biomarkers." She adds that "liquid biopsy enables us to obtain the molecular information needed to make the most appropriate clinical decisions more quickly, using a procedure as straightforward as a blood test."
En el trabajo han colaborado investigadores del área de investigación en cáncer del área del CIBER del cáncer (CIBERONC). Los centros participantes han sido el Hospital del Mar, el Hospital Vall d'Hebron y el Hospital Clínic de Barcelona, el Hospital Universitario 12 de Octubre, HM Sanchinarro, la Fundación Jiménez Díaz y el Hospital Sanitas-Zarzuela de Madrid, la Clínica Universidad de Navarra y el Hospital Universitario de Burgos. El estudio se ha hecho en colaboración con la empresa Guardant Health, en Palo Alto, California, en los Estados Unidos.
Researchers from the cancer research area of the Spanish Biomedical Research Network in Cancer, CIBERONC, also participated in the study. The participating centres were Hospital del Mar, Vall d'Hebron University Hospital and Hospital Clínic de Barcelona; Hospital Universitario 12 de Octubre, HM Sanchinarro, Fundación Jiménez Díaz and Hospital Sanitas La Zarzuela in Madrid; Clínica Universidad de Navarra; and Hospital Universitario de Burgos. The study was carried out in collaboration with Guardant Health, based in Palo Alto, California, United States.
Reference article
Visa L, Badia-Ramentol J, Fernández MC, Saurí T, Macias I, Zhang N, Adeva J, Zumstein L, Peinado P, Ponz-Sarvisé M, Ceniceros L, Fabregat-Franco C, Caramés C, Lopez AM, Salinas P, Monzonis X, Masfarré L, Sibilio A, Riva F, Cubillo A, Faull I, Macarulla T, Iglesias M, Bellosillo B, Montagut C. Next generation sequencing of circulating tumor DNA for precision medicine in patients with advanced biliary tract cancers. Clin Cancer Res. 2026 Jun 1. doi: 10.1158/1078-0432.CCR-26-0096. Epub ahead of print. PMID: 42223536.
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