@article{bibcite_8756,
  author = {Hui-Hsuan Kuo and Bhavneet Bhinder and Hamza N. Gokozan and Kathryn Gorski and Pooja Chandra and Jyothi Manohar and Daniela Guevara and John Otilano and Jenna Moyer and Marvel Tranquille and Sarah Ackermann and Jared Capuano and Cynthia Cheung and Thomas A. Caiazza and Phoebe L. Reuben and Anastasia Murray Tsomides and Adriana Irizarry and Michael Sigouros and David Wilkes and Abigail King and Troy Kane and Majd Al Assaad and Wael Al Zoughbi and Kentaro Ohara and Joonghoon Auh and Peter Waltman and Florencia P. Madorsky Rowdo and Enrique Podaza and Valerie Gallegos and John Nguyen and Raehash Shah and Manish Shah and Allyson Ocean and Douglas Scherr and Nasser Altorki and Melissa Frey and Ana M. Molina and Lisa Newman and Vivan Bea and Eloise Chapman-Davis and Marcus D. Goncalves and Ashish Saxena and Parul J. Shukla and Kevin Holcomb and Rachel Simmons and Scott Tagawa and Jonathan H. Zippin and Evelyn Cantillo and Rohit Chandwani and Melissa Davis and Kelly Garrett and Pashtoon M. Kasi and Jennifer Marti and David Nanus and Jones T. Nauseef and Elizabeth Popa and Momin T. Siddiqui and Alicia Alonso and Cora N. Sternberg and Bishoy M. Faltas and Olivier Elemento and Juan Miguel Mosquera and Andrea Sboner and M. Laura Martin},
  title = {Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities},
  abstract = {We developed a pan-cancer patient-derived organoid (PDO) platform comprising 220 PDOs from 191 patients across 15 cancer types to advance functional precision oncology. Comprehensive characterization demonstrated high fidelity to parent tumors, with 93\% histopathology concordance, 80\% median genomic concordance for driver mutations, and a 0.85 median gene expression correlation. Expression profiles remained largely stable over 10 passages, ensuring reproducibility for long-term screening. Clonality analysis showed that 85\% of dominant tumor clones were preserved, with genomic concordance directly reflecting clonal similarity. Even PDOs with lower concordance retained key oncogenic drivers, validating their utility as disease models. Functional assays revealed that 58\% of PDOs from patients ineligible for US Food and Drug Administration{\textendash}approved poly(adenosine 5'-diphosphate{\textendash}ribose) polymerase inhibitors were sensitive to talazoparib, linked to DNA damage repair alterations. Furthermore, combination screens identified agents that overcome resistance, particularly in TP53-mutant models. Our platform enables the investigation of targeted therapies and molecular drivers of drug sensitivity, providing translational insights for personalized treatment beyond current biomarker guidelines.},
  year = {2026},
  journal = {Science Advances},
  volume = {12},
  pages = {eadz3351},
  month = {2026-06-26},
  url = {https://www.science.org/doi/10.1126/sciadv.adz3351},
  doi = {10.1126/sciadv.adz3351},
}