Developing patient-derived organoids to predict PARP inhibitor response and explore resistance overcoming strategies in ovarian cancer

Tao, Mengyu; Sun, Fan; Wang, Juan; Wang, Yujing; Zhu, Hongrui; Chen, Meiqi; Liu, Liyun; Liu, Li; Lin, Hou‐Wen; Wu, Xia

doi:10.1016/j.phrs.2022.106232

Cited by 18 publications

(19 citation statements)

References 48 publications

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“…As underlined in the previous paragraph of our review, the OC PDOs recapitulated the main hallmarks of the original tumor, including CNVs, recurrent mutations, and tumor heterogeneity, while also providing the opportunity to test drug therapy [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In fact, the authors demonstrated that the drug–response curves revealed distinct sensitivities of the different PDO lines for the drugs, indicating patients’ tumor-dependent responses and highlighting the potential applicability of EOC-derived organoids as a drug screening platform [ 32 , 34 , 36 , 38 , 40 ].…”

Section: Drug Screeningmentioning

confidence: 97%

“…Several studies have reported on different types of genomic characterization used to compare native tumor tissues and PDOs, demonstrating that OC PDOs capture tumor heterogeneity such as nuclear and cellular atypia, as well as biomarker expression [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] (see Table 1 for details).…”

Section: Patient-derived Organoids (Pdos)mentioning

confidence: 99%

“…To further quantify the genetic correlation between PDOs and corresponding native tumors, the authors analyzed S-SNVs and structural variants (SVs). PDOs recapitulated the total mutational load and the different contributions of point mutation types of corresponding tumors with a 91.5% overlap [ 44 ].…”

Section: Patient-derived Organoids (Pdos)mentioning

confidence: 99%

“…Matrigel may also contain collagens I, XVIII, VI, and III, alongside growth factors and enzymes such as TGF-β, FGF, and matrix metalloproteinases (MMPs) [ 27 , 48 ]. Matrigel was used as a 3D ECM scaffold in the current studies, with cells cultured in a cocktail of growth and signaling factors (see Table 2 for details) [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Some authors described their personal cocktail of growth and signaling factors, with the establishment of OC PDOs in culture taking from 1 to 4 weeks.…”

Section: Extracellular Matrix (Ecm) and Tumor Microenvironment (Tme)mentioning

confidence: 99%

“…One of the most important applications of drug screening in PDOs was the ability to test PARPi [ 31 , 32 , 34 , 35 , 44 ]. HRD cells have been shown to be sensitive to PARP inhibitors, and the HRD mutational signature of PDOs could predict sensitivity to PARPi treatment in both PDOs and the primary tumor [ 26 ].…”

Section: Drug Screeningmentioning

confidence: 99%

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Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine

Spagnol

Sensi

Tommasi

et al. 2023

Cancers

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Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to the high prevalence of advanced stages of diagnosis and the high rate of recurrence. Furthermore, the heterogeneity of OC tumors contributes to the rapid development of resistance to conventional chemotherapy. In recent years, in order to overcome these problems, targeted therapies have been introduced in various types of tumors, including gynecological cancer. However, the lack of predictive biomarkers showing different clinical benefits limits the effectiveness of these therapies. This requires the development of preclinical models that can replicate the histological and molecular characteristics of OC subtypes. In this scenario, organoids become an important preclinical model for personalized medicine. In fact, patient-derived organoids (PDO) recapture tumor heterogeneity with the possibility of performing drug screening. However, to best reproduce the patient’s characteristics, it is necessary to develop a specific extracellular matrix (ECM) and introduce a tumor microenvironment (TME), which both represent an actual object of study to improve drug screening, particularly when used in targeted therapy and immunotherapy to guide therapeutic decisions. In this review, we summarize the current state of the art for the screening of PDOs, ECM, TME, and drugs in the setting of OC, as well as discussing the clinical implications and future perspectives for the research of OC organoids.

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Section: Drug Screeningmentioning

confidence: 97%

Section: Patient-derived Organoids (Pdos)mentioning

confidence: 99%

Section: Patient-derived Organoids (Pdos)mentioning

confidence: 99%

Section: Extracellular Matrix (Ecm) and Tumor Microenvironment (Tme)mentioning

confidence: 99%

Section: Drug Screeningmentioning

confidence: 99%

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Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine

Spagnol

Sensi

Tommasi

et al. 2023

Cancers

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The recent advance and prospect of poly(ADP‐ribose) polymerase inhibitors for the treatment of cancer

Bai,

Yang,

Jia

et al. 2024

Medicinal Research Reviews

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Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long‐term medication‐induced drug resistance. Poly(ADP‐ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP‐DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first‐line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure–activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

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Establishment of matched bladder cancer PDX and PDX-derived organoid model and evaluation of anti-tumor efficacy of abemaciclib

Lu,

Hu,

Duan

et al. 2024

Clin Transl Oncol

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Developing patient-derived organoids to predict PARP inhibitor response and explore resistance overcoming strategies in ovarian cancer

Cited by 18 publications

References 48 publications

Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine

Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine

The recent advance and prospect of poly(ADP‐ribose) polymerase inhibitors for the treatment of cancer

Establishment of matched bladder cancer PDX and PDX-derived organoid model and evaluation of anti-tumor efficacy of abemaciclib

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