TY - JOUR
AU - Hui-Hsuan Kuo
AU - Bhavneet Bhinder
AU - Hamza N. Gokozan
AU - Kathryn Gorski
AU - Pooja Chandra
AU - Jyothi Manohar
AU - Daniela Guevara
AU - John Otilano
AU - Jenna Moyer
AU - Marvel Tranquille
AU - Sarah Ackermann
AU - Jared Capuano
AU - Cynthia Cheung
AU - Thomas A. Caiazza
AU - Phoebe L. Reuben
AU - Anastasia Murray Tsomides
AU - Adriana Irizarry
AU - Michael Sigouros
AU - David Wilkes
AU - Abigail King
AU - Troy Kane
AU - Majd Al Assaad
AU - Wael Al Zoughbi
AU - Kentaro Ohara
AU - Joonghoon Auh
AU - Peter Waltman
AU - Florencia P. Madorsky Rowdo
AU - Enrique Podaza
AU - Valerie Gallegos
AU - John Nguyen
AU - Raehash Shah
AU - Manish Shah
AU - Allyson Ocean
AU - Douglas Scherr
AU - Nasser Altorki
AU - Melissa Frey
AU - Ana M. Molina
AU - Lisa Newman
AU - Vivan Bea
AU - Eloise Chapman-Davis
AU - Marcus D. Goncalves
AU - Ashish Saxena
AU - Parul J. Shukla
AU - Kevin Holcomb
AU - Rachel Simmons
AU - Scott Tagawa
AU - Jonathan H. Zippin
AU - Evelyn Cantillo
AU - Rohit Chandwani
AU - Melissa Davis
AU - Kelly Garrett
AU - Pashtoon M. Kasi
AU - Jennifer Marti
AU - David Nanus
AU - Jones T. Nauseef
AU - Elizabeth Popa
AU - Momin T. Siddiqui
AU - Alicia Alonso
AU - Cora N. Sternberg
AU - Bishoy M. Faltas
AU - Olivier Elemento
AU - Juan Miguel Mosquera
AU - Andrea Sboner
AU - M. Laura Martin
AB - 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–approved poly(adenosine 5′-diphosphate–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.
BT - Science Advances
DA - 2026-06-26
DO - 10.1126/sciadv.adz3351
IS - 26
N2 - 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–approved poly(adenosine 5′-diphosphate–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.
PY - 2026
EP - eadz3351
T2 - Science Advances
TI - Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities
UR - https://www.science.org/doi/10.1126/sciadv.adz3351
VL - 12
Y2 - 2026-07-22
ER -