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Journal
Description
For the right cancer medicine, ask the tumor. Seattle’s SEngine is using patient tumor samples to derive cancer organoids for accurate ex vivo drug testing, target identification and drug development.
Although many people think of cancer as a single disease, in reality, it is a collection of many different diseases. Each patient’s cancer is a unique mosaic of genetic and epigenetic alterations, which is why it has been a challenge to identify the right course of therapies for each patient.
A cancer organogram test as a guide for oncology treatments in SOLID tumors: An analysis of 628 tests in 419 patients, Astrid Margossian et al.
This study demonstrates a strong clinical prediction of the “cancer organogram” for targeted and chemotherapeutic agents. The organogram guided selection of therapeutics for a significant subset of cancer patients, nearly 4 times the rate reported with genomic testing alone.
Functional drug screening of organoids from ovarian cancer patients demonstrates clinical and genomic concordance and identifies novel therapeutic vulnerabilities, Goldie Lui et al.
The genomic/histopathological heterogeneity and unique patterns of drug responses across cancer patients highlight the need to individualize therapy. This study data demonstrates the utility of organoid based drug screening to nominate therapeutic options for individual patients with or without known genomic biomarkers.
Targeting BET Proteins BRD2 and BRD3 in Combination with PI3K-AKT Inhibition as a Therapeutic Strategy for Ovarian Clear Cell Carcinoma, Shogo Shigeta et al.
This study identifies novel drug targets and combinations to combat ovarian clear cell carcinoma (OCCC). Co-authored by researchers from the Fred Hutchinson Cancer Research Center, SEngine Precision Medicine, Weill Cornell Medicine, and the University of Washington.
BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer, Goldie Lui et al.
This study shows conditional high-throughput siRNA and drug screening of ovarian cancer PDCs that faithfully recapitulate patient tumour genetics and biology to identify and prioritize effective target and drug combinations with PARPi for HGSC and OCCC.
Organoid based functional test to predict personalized treatment in cholangiocarcinoma, Franz X. Schaub et al.
This study shows the feasibility of functional testing of organoids derived from cholangiocarcinoma patients in a CLIA certified diagnostic test.
Organoid based functional test to predict personalized treatment in cholangiocarcinoma, Astrid Margossian, Carla Grandori et al.
This study shows the potential clinical utility of high throughput pharmacogenomic profiling of organoids derived from patients with cholangiocarcinoma in a CLIA certified diagnostic test.
Predictive value of a CLIA approved organoid based drug sensitivity test, Astrid Margossian, Carla Grandori et al.
This study shows the strong concordance with genomic and retrospective clinical evidence of CLIA certified pharmacogenomic profiling of organoids derived from patients with a range of solid tumors.
Clinical and genomic correlation of a CLIA certified organoid based functional test in breast cancer patients, Astrid Margossian et al.
This study shows organoid based drug testing exhibits strong concordance with genomic or IHC biomarkers and clinical response.
Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases to direct personalized therapy, Narasimhan et al.
This study demonstrates the feasibility and potential clinical utility of pharmacogenomic profiling of organoids derived from late-stage colorectal cancer patients and identifies potential therapies for a subset of patients with no remaining options.
The Promise of Functional Precision Medicine, Christopher Kemp, Carla Grandori
This invited interview with Drs. Kemp and Grandori describes the techniques, uses and challenges of functional testing to guide precision medicine.
Personalized Cancer Models for Target Discovery and Precision Medicine - A Review, Carla Grandori et al.
This invited review outlines the enormous potential of using patient derived tumor models for target discovery, drug development, cancer biology, and clinical utility.
Patient derived organoids to model rare prostate cancer phenotypes, Puca et al.
This study demonstrates the utility of pharmacogenomic profiling of organoids and identifies potential therapies.
A Phase I Clinical Trial of AZD1775 in Combination With Neoadjuvant Weekly Docetaxel and Cisplatin Before Definitive Therapy in Head and Neck Squamous Cell Carcinoma, Eduardo Mendez et al.
This study describes results of a clinical trial using a targeted WEE1 inhibitor in patients with borderline respectable head and neck cancer. Although this was only a toxicity finding study, nine out ten patients showed an objective response. Further, this study highlights the ability of our drug target discovery platform to drive clinical trials.
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas, Franz X. Schaub, et al.
This landmark TCGA study provides the most comprehensive analysis of alterations in the MYC oncogene across all cancers. This resource will guide basic and clinical research, particularly for development of novel therapies to treat MYC driven cancers.
Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine, Chantal Pauli et al.
Featured as highlight for this issue and profiled in Nature Medicine and Nature. This study describes the utility of using pharmacogenomic profiling of tumor derived organoids to identify potential therapeutic options. Whole exome sequencing of late-stage cancers identified alterations with a potential matching drug in less than 5% of cases. In contrast, drug profiling found multiple potentially effective drugs for every patient tested, as well as novel drug combinations.
Synthetic lethal screens as a means to understand and treat MYC-driven cancers, Silvia Cermelli et al.
This invited review highlights the use of novel isogenic cell systems and an arrayed siRNA screening platform to identify genes that are synthetic lethal to common human oncogenes.
Functional genomics to identify unforeseen cancer drug targets Chris Kemp et al.
This invited review discusses the potential of unbiased genome scale functional genomic screens to identify novel drug targets.