Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Май 10, 2021

While the potential of patient-derived organoids (PDOs) to predict patients' responses anti-cancer treatments has been well recognized, lengthy time and low efficiency in establishing PDOs hamper implementation PDO-based drug sensitivity tests clinics. We first adapt a mechanical sample processing method generate lung cancer (LCOs) from surgically resected biopsy tumor tissues. The LCOs recapitulate histological genetic features parental tumors have expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds LCOs, number that can be generated most samples at passage 0, are sufficient produce clinically meaningful within week. results prove our one-week good agreement with xenografts, mutations tumors, clinical outcomes. LCO model coupled device provides technically feasible means for predicting patient-specific settings.

Язык: Английский

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Patient-derived organoids as a predictive biomarker for treatment response in cancer patients

npj Precision Oncology, Год журнала: 2021, Номер 5(1)

Опубликована: Апрель 12, 2021

Abstract Effective predictive biomarkers are needed to enable personalized medicine and increase treatment efficacy survival for cancer patients, thereby reducing toxic side effects costs. Patient-derived organoids (PDOs) individualized tumour response testing. Since 2018, 17 publications have examined PDOs as a potential biomarker in the of patients. We review provide pooled analysis results regarding use testing, focusing on evidence analytical validity, clinical validity utility. identify future perspectives accelerate implementation

Язык: Английский

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Signaling pathways and therapeutic interventions in gastric cancer

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Окт. 8, 2022

Abstract Gastric cancer (GC) ranks fifth in global diagnosis and fourth cancer-related death. Despite tremendous progress therapeutic strategies significant improvements patient survival, the low malignancy stage is relatively asymptomatic many GC cases are diagnosed at advanced stages, which leads to unsatisfactory prognosis high recurrence rates. With recent advances genome analysis, biomarkers have been identified that clinical importance for diagnosis, treatment, prognosis. Modern molecular classifications uncovered vital roles signaling pathways, including EGFR/HER2, p53, PI3K, immune checkpoint cell adhesion molecules, play tumorigenesis, progression, metastasis, responsiveness. These open way more precise diagnoses treatments patients. Nevertheless, relative significance, temporal activation, interaction with risk factors, crosstalk between these pathways not well understood. Here, we review regulatory of potential biomarkers, targets an emphasis on discoveries. Current therapies, signaling-based immunotherapies exploited past decade, development treatment GC, particularly challenges developing precision medications, discussed. provide a direction integration clinical, molecular, genomic profiles improve treatments.

Язык: Английский

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Mismatch Repair–Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy

Clinical Cancer Research, Год журнала: 2020, Номер 26(13), С. 3271 - 3279

Опубликована: Март 6, 2020

Abstract Purpose: Evaluate response of mismatch repair–deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. Experimental Design: dMMR tumors at Memorial Sloan Kettering Cancer Center (New York, NY) were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty patients with identified by IHC and/or microsatellite instability analysis, initial treatment compared a matched MMR-proficient (pMMR) cohort. Germline somatic mutation analyses evaluated. Patient-derived tumoroids assessed chemotherapy sensitivity. Results: Of 21 receiving (fluorouracil/oxaliplatin), six (29%) had progression disease. In comparison, no was noted in 63 pMMR (P = 0.0001). Rectal reflected this resistance No genomic predictors identified. 16 chemoradiation, 13 (93%) experienced tumor downstaging; one patient stable disease, comparable 48 cancers. undergoing surgery, 12 (92%) early-stage Forty-two (84%) the 50 tested positive Lynch syndrome enrichment germline MSH2 MSH6 mutations when 193 syndrome–associated colon (MSH2, 57% vs 36%; MSH6, 17% 9%; P < 0.003). Conclusions: Over one-fourth treated exhibited disease progression. Conversely, sensitive chemoradiation. MMR status should be performed upfront all locally advanced careful monitoring on genetic testing cancer.

Язык: Английский

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Artificial intelligence aids in development of nanomedicines for cancer management

Seminars in Cancer Biology, Год журнала: 2023, Номер 89, С. 61 - 75

Опубликована: Янв. 20, 2023

Язык: Английский

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Rational Cancer Treatment Combinations: An Urgent Clinical Need

Molecular Cell, Год журнала: 2020, Номер 78(6), С. 1002 - 1018

Опубликована: Июнь 1, 2020

Язык: Английский

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Organoid models of gastrointestinal cancers in basic and translational research

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2020, Номер 17(4), С. 203 - 222

Опубликована: Фев. 25, 2020

Язык: Английский

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Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy

Clinical Cancer Research, Год журнала: 2020, Номер 26(14), С. 3662 - 3670

Опубликована: Май 6, 2020

Abstract Purpose: Patients with colorectal cancer peritoneal metastases (CRPMs) have limited treatment options and the lowest survival rates. We aimed to determine whether organoid testing could help guide precision for patients CRPMs, as clinical utility of prospective, functional drug screening including nonstandard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from underwent parallel next-generation sequencing medium-throughput panel ex vivo identify specific sensitivities each patient. measured such a service including: success peritonoid generation, time cultivate peritonoids, reproducibility testing, documented changes therapy result testing. Results: Peritonoids were successfully generated validated 68% (19/28) undergoing standard care. Genomic profiling was completed within 8 weeks formal report ranking provided medical oncology team upon failure care treatment. This resulted in change two patients, one whom had partial response despite previously progressing on multiple rounds chemotherapy. The barrier implementing this technology Australia need access funding off-label indications. Conclusions: Our approach feasible, reproducible, can novel therapeutic choices poor prognosis cohort, where new are urgently needed. platform relevant many solid organ malignancies.

Язык: Английский

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Human disease models in drug development

Nature Reviews Bioengineering, Год журнала: 2023, Номер 1(8), С. 545 - 559

Опубликована: Май 11, 2023

Язык: Английский

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Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Окт. 30, 2020

Abstract Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential improving therapeutic outcomes. However, current machine-learning-based predictions of response often fail to identify robust translational from preclinical models. Here, we present a machine-learning framework by taking advantage network-based analyses pharmacogenomic data derived three-dimensional organoid culture The identified our approach accurately predict the 114 colorectal cancer patients treated with 5-fluorouracil and 77 bladder cisplatin. We further confirm external transcriptomic datasets drug-sensitive -resistant isogenic cell lines. Finally, concordance analysis between independent somatic mutation-based validate method. This work presents method models combining application gene modules approaches.

Язык: Английский

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