The promise of patient-derived organoid models in precision medicine for biliary tract cancer

Biliary tract cancer (BTC) poses a distinctive challenge in oncology, mainly due to diagnosis at late-stage and limited effective systemic treatment options. Chemotherapy serves as the primary therapy for patients, with variable responses and a dismal survival rate. There is therefore an urgent need to advance cancer modelling to better predict which patients would be most likely to respond to chemotherapy and those who will develop resistance.

Preclinical patient-derived organoids (PDOs) provide a reliable 3D in vitro model that closely recapitulates the original tumor, representing a predictive biomarker for treatment response in cancer patients. Compared to alternative patient-derived models, such as patient-derived xenografts (PDXs), PDOs constitute a cost-effective platform for high-throughput anti-cancer drug discovery.

Published as an invited Preview article in the open access journal Cell Reports Medicine ⁽¹⁾, investigators of VHIO’s Upper Gastrointestinal Cancer Translational Research Group highlight a research paper published in the same issue of the journal by Ren et al.⁽²⁾ presenting a novel collection of 61 BTC PDO models. The study shows that these models accurately capture the histopathologic and genomic features of their original tumors and could potentially serve as predictive biomarkers for BTC patient responses to chemotherapy.

“This study presents a valuable platform of biliary tract cancer patient-derived organoids and demonstrates the potential of these models as tools for advancing precision medicine in biliary tract cancer,” says Mariana Yáñez-Bartolomé, a PhD Student of VHIO’s Upper Gastrointestinal Cancer Translational Research Group and first author of this Preview article.

“While numerous BTC PDO collections have been documented, the utilization of large-scale collections for cancer modeling and predicting treatment responses in these patients remains limited,” adds Teresa Macarulla, Principal Investigator of the same VHIO group and Head of the Upper Gastrointestinal and Endocrine Tumors Unit at the Vall d’Hebron University Hospital (HUVH).

The study authors propose the use of gene panels to effectively distinguish patients who exhibit a favorable response to chemotherapy from those who do not. Findings underscore the potential utility of biomarker panels obtained from BTC PDOs to provide accurate predictions of patient responses to treatment.

As VHIO investigators highlight in their review, while these models could also provide crucial insights into tumor characteristics and drug responses, they have their limitations.

“The long-term maintenance of BTC PDO is an important issue, requiring a deeper exploration of the clinical, genomic, and transcriptional factors contributing to sustained growth. In addition, the specificity and sensitivity of the proposed gene panels will need to be validated in larger and independent patient cohorts,” concludes Tian Tian, senior author of the Preview article and preclinical team leader of VHIO’s Upper Gastrointestinal Cancer Translational Research Group.

References

Yáñez-Bartolomé M, Macarulla T, Tian TV. Potential of Patient-Derived Organoids in Precision Medicine of Biliary Tract Cancer. Cell Rep Med. Vol 4, Issue 11, 101294, Nov 2023. https://doi.org/10.1016/j.xcrm.2023.101294

Ren X, Huang M, Weng W, Xie Y, Wu Y, Zhu S, Zhang Y, Li D, Lai J, Shen S, Lin J, Kuang M, Li X, Yu J, Xu L. Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application. Cell Rep Med. 2023 Nov Vol 4, Issue 11, 101277. Nov 2023, https://doi.org/10.1016/j.xcrm.2023.101277