Lung cancer organoids: models for preclinical research and precision medicine DOI Creative Commons
Yajing Liu, Yanbing Zhou, Pu Chen

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Окт. 24, 2023

Lung cancer is a malignancy with high incidence and mortality rates globally, it has 5-year survival rate of only 10%–20%. The significant heterogeneity in clinical presentation, histological features, multi-omics findings, drug sensitivity among different lung patients necessitate the development personalized treatment strategies. current precision medicine for cancer, primarily based on pathological genomic testing, fails to meet needs clinically refractory cancer. organoids (LCOs) are derived from tumor cells within tissues generated through three-dimensional tissue culture, enabling them faithfully recapitulate vivo characteristics heterogeneity. establishment series LCOs biobanks offers promising platforms efficient screening identification novel targets anti-tumor discovery. Moreover, provide supplementary decision-making factors enhance thereby addressing limitations associated pathology-guided approaches managing This article presents comprehensive review construction methods potential applications both preclinical research. It highlights significance biomarker exploration, resistance investigation, target identification, screening, as well microfluidic technology-based high-throughput Additionally, discusses future prospects this field.

Язык: Английский

Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma DOI Creative Commons
Alexandra Lahtinen, Kari Lavikka, Anni Virtanen

и другие.

Cancer Cell, Год журнала: 2023, Номер 41(6), С. 1103 - 1117.e12

Опубликована: Май 18, 2023

Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients HGSC prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features genomics, pathways, morphological phenotypes, significant association treatment response. Nested pathway analysis suggests two trajectories between states. Experiments five tumor organoids PI3K inhibitors support targeting enriched PI3K/AKT alpelisib. Heterogeneity anatomical sites shows that site-of-origin 70% more unique than metastatic or ascites. In conclusion, these visualization methods enable integrative evolution to identify patient subtypes cohorts.

Язык: Английский

Процитировано

53
Single-cell transcriptomes identify patient-tailored therapies for selective co-inhibition of cancer clones DOI Creative Commons
Aleksandr Ianevski, Kristen Nader,

Kyriaki Driva

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 3, 2024

Язык: Английский

Процитировано

12
Oncogenic Pathways and Targeted Therapies in Ovarian Cancer DOI Creative Commons

Carolina Lliberos,

Gary Richardson, Antonella Papa

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 585 - 585

Опубликована: Май 15, 2024

Epithelial ovarian cancer (EOC) is one of the most aggressive forms gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as patients are advanced disease. Debulking surgery and platinum-based therapies current mainstay treatment. However, despite achieving initial remission, a significant portion will relapse because innate acquired resistance, at which point disease considered incurable. In view this, novel detection strategies therapeutic approaches needed to improve outcomes survival patients. this review, we summarize our knowledge genetic landscape molecular pathways underpinning its many subtypes. By examining explored in preclinical clinical settings, highlight importance decoding how single convergent alterations co-exist drive progression resistance treatments. We also propose that core signalling such PI3K MAPK play critical roles origin diverse subtypes can become new targets combination known DNA damage repair development tailored more effective anti-cancer

Язык: Английский

Процитировано

9
Homologous Recombination Deficiency Unrelated to Platinum and PARP Inhibitor Response in Cell Line Libraries DOI Creative Commons
Shiro Takamatsu, Kosuke Murakami, Noriomi Matsumura

и другие.

Scientific Data, Год журнала: 2024, Номер 11(1)

Опубликована: Фев. 6, 2024

Abstract While large publicly available cancer cell line databases are invaluable for preclinical drug discovery and biomarker development, the association between homologous recombination deficiency (HRD) sensitivity in these resources remains unclear. In this study, we comprehensively analyzed molecular profiles screening data from Cancer Cell Line Encyclopedia. Unexpectedly, gene alterations BRCA1/2 or recombination-related genes, HRD scores, mutational signature 3 were not positively correlated with to platinum agents PARP inhibitors. Rather, higher scores significantly associated resistance multiple assays. These findings consistent when analyzing exclusively breast ovarian lines using COSMIC Project. Collectively, existing established do reflect expected status response inhibitors clinical tumors. This discrepancy may extend other tumor characteristics, highlighting importance of recognizing potential limitations researchers.

Язык: Английский

Процитировано

8
Organoids in ovarian cancer: a platform for disease modeling, precision medicine, and drug assessment DOI Creative Commons

Haiyao Hu,

Chongen Sun,

Jingyao Chen

и другие.

Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 150(3)

Опубликована: Март 20, 2024

Abstract Ovarian cancer (OC) is a major cause of gynecological mortality, necessitating enhanced research. Organoids, cellular clusters grown in 3D model, have emerged as disruptive paradigm, transcending the limitations inherent to conventional models by faithfully recapitulating key morphological, histological, and genetic attributes. This review undertakes comprehensive exploration potential organoids derived from murine, healthy population, patient origins, encompassing spectrum that spans foundational principles pioneering applications. Organoids serve preclinical models, allowing us predict how patients will respond treatments guiding development personalized therapies. In context evaluating new drugs, act versatile platforms, enabling thorough testing innovative combinations novel agents. Remarkably, mimic dynamic nature OC progression, its initial formation spread other parts body, shedding light on intricate details hold significant importance. By functioning at an individualized level, uncover complex mechanisms behind drug resistance, revealing strategic opportunities for effective treatments.

Язык: Английский

Процитировано

6
Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine DOI Creative Commons
Qigu Yao, Sheng Cheng, Qiaoling Pan

и другие.

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 21, 2024

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions specific organs. Although field organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, bioinstrumentation, a comprehensive overview organoid applications remains necessary. This review offers detailed exploration historical origins characteristics various types, their applications-including disease modeling, drug toxicity efficacy assessments, precision medicine, regenerative medicine-as well as current challenges future directions research. have proven instrumental elucidating genetic cell fate hereditary diseases, infectious metabolic disorders, malignancies, study processes such embryonic development, molecular mechanisms, host-microbe interactions. Furthermore, integration technology with intelligence microfluidics significantly advanced large-scale, rapid, cost-effective thereby propelling progress medicine. Finally, advent high-performance materials, three-dimensional printing technology, also gaining prominence Our insights predictions aim to provide valuable guidance researchers support continued advancement this rapidly developing field.

Язык: Английский

Процитировано

6
Organoid: Bridging the gap between basic research and clinical practice DOI
Guihu Weng, Jinxin Tao, Yueze Liu

и другие.

Cancer Letters, Год журнала: 2023, Номер 572, С. 216353 - 216353

Опубликована: Авг. 18, 2023

Язык: Английский

Процитировано

14
Patient‐derived ovarian cancer organoid carries immune microenvironment and blood vessel keeping high response to cisplatin DOI Creative Commons
Yuqing Zhao, Chen Wang, Wei Deng

и другие.

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Авг. 28, 2024

Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian was High-Grade Serous Cancer. However, Cancer organoid rare, which with patient immune microenvironment blood vessels even absence. Here, we report a novel system derived from samples. These organoids recapitulate organoids' histological molecular heterogeneity while preserving the critical vessels, as evidenced by presence of

Язык: Английский

Процитировано

5
Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications DOI Creative Commons

Colin D. Paul,

Chris Yankaskas,

Pradip Shahi Thakuri

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 31, 2025

Язык: Английский

Процитировано

0
Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma DOI Creative Commons
Jan Benada, Daria Bulanova, Violette Azzoni

и другие.

NAR Cancer, Год журнала: 2023, Номер 5(3)

Опубликована: Июнь 9, 2023

Abstract Ovarian cancer is driven by genetic alterations that necessitate protective DNA damage and replication stress responses through cell cycle control genome maintenance. This creates specific vulnerabilities may be exploited therapeutically. WEE1 kinase a key kinase, it has emerged as promising therapy target. However, adverse effects have limited its clinical progress, especially when tested in combination with chemotherapies. A strong interaction between PKMYT1 led us to hypothesize multiple low-dose approach utilizing joint inhibition would allow exploitation of the synthetic lethality. We found exhibited synergistic eradicating ovarian cells organoid models at low dose. The synergistically promoted CDK activation. Furthermore, combined treatment exacerbated catastrophe, leading increase genomic instability inflammatory STAT1 signalling These findings suggest new harness potency lethal contribute development treatments for cancer.

Язык: Английский

Процитировано

11