Dataset Information

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

ABSTRACT: Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.

SUBMITTER: Risbridger GP

PROVIDER: S-EPMC8376965 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Risbridger Gail P GP Clark Ashlee K AK Porter Laura H LH Toivanen Roxanne R Bakshi Andrew A Lister Natalie L NL Pook David D Pezaro Carmel J CJ Sandhu Shahneen S Keerthikumar Shivakumar S Quezada Urban Rosalia R Papargiris Melissa M Kraska Jenna J Madsen Heather B HB Wang Hong H Richards Michelle G MG Niranjan Birunthi B O'Dea Samantha S Teng Linda L Wheelahan William W Li Zhuoer Z Choo Nicholas N Ouyang John F JF Thorne Heather H Devereux Lisa L Hicks Rodney J RJ Sengupta Shomik S Harewood Laurence L Iddawala Mahesh M Azad Arun A AA Goad Jeremy J Grummet Jeremy J Kourambas John J Kwan Edmond M EM Moon Daniel D Murphy Declan G DG Pedersen John J Clouston David D Norden Sam S Ryan Andrew A Furic Luc L Goode David L DL Frydenberg Mark M Lawrence Mitchell G MG Taylor Renea A RA

Nature communications 20210819 1

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumor ...[more]

PMID: 34413304

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Project description:Background and objectiveMulti-photon microscopy (MPM) is a 3-dimension fluorescence imaging technique that combines the excitation of two low-energy photons, enabling less photo-bleaching and deeper penetration of the imaged tissue. Two signals are detected, autofluorescence (AF), from natural intracellular fluorophores [such as nicotinamide adenine dinucleotide phosphate (NADP) and flavine adenine dinucleotide (FAD) transformation], and second harmonic generation (SHG), a physical property of the laser enhancing non-centrosymmetric structures such as collagen fibers. MPM can give both visual and quantitative information of a fresh tissue (without the need of processing, cutting or staining the tissue), aiding in the progress towards optimizing a real-time imaging device. The objective of this review is to show the value and benefits of the use of MPM in uro-oncology.MethodsA structured literature review was performed using PubMed and Web of Sciences, including all articles with the following keywords: "multiphoton microscopy", "two-photon microscopy", "non-linear microscopy", "second harmonic generation", "urology", "prostate", "bladder", "kidney", "upper tract", "oncology", "surgical margins", "frozen section". Articles were reviewed to summarize the use of this tool in performing biopsies, assessing surgical margins, staging and grading complementary tool, and real-time imaging.Key content and findingsA total of 476 articles were identified with these keywords, and later screened for inclusion. We finally included 47 publications that were relevant to our topic. The advantages of this technique have led to its application in the management of several cancers, allowing cellular description as well as quantitative measurements of AF or SHG and their correlation with clinical outcomes.ConclusionsMPM has shown great improvement in providing a real time assessment of fresh tissue, giving oncologic diagnosis, performing in vivo imaging and quantitative analysis of the tissue as well as increasing precision of the diagnosis. This nonlinear optical technique has the potential of guiding both biopsy and surgery, as well as helping the surgeon with interesting additional tissue information intra-operatively.

Project description:BackgroundTelehealth services are rapidly embraced in uro-oncology due to the current coronavirus disease 2019 (COVID-19) pandemic.ObjectiveTo determine patients' perspective on adoption of telehealth as a response to the pandemic and its sustainability in the future.Design, setting, and participantsFollowing a COVID-19 outbreak, 101 patients with advanced genitourinary cancers are currently managed "virtually" for therapy administration at our tertiary care unit. They were surveyed about the current situation, and current and long-term employment of telehealth.InterventionRapid implementation of virtual patient management.Outcome measurements and statistical analysisPatients' perception of anxiety of COVID-19 and cancer, perspective on telehealth measures as a reaction to the current COVID-19 pandemic, and long-term acceptance were used as outcomes. Wilcoxon matched-pair signed rank test, chi-square test, and Mann-Whitney U test were performed.Results and limitationsOf 101 patients, 92 answered the questionnaire, with 71 (77.2%) responding virtually by e-mail or phone call. Anxiety of cancer (6/10, interquartile range [IQR] 3-8) superseded that of COVID-19 (four/10, IQR 2-5.25, p<0.001), and patients oppose temporary treatment interruption. Of the patients, 66.0% perceive their susceptibility to COVID-19 as equal to or lower than the general population and 52.2% believe that COVID-19 will not affect their therapy. In future, patients (62.6%) prefer to maintain in-person appointments as opposed to complete remote care, but accept remote care during the pandemic (eight/10, IQR 5-9). Beyond the crisis, maintaining telehealth has low preference rates (four/10, IQR 2-7), with high acceptance for external laboratory controls (60.9%) and online visit management (48.9%), but lower acceptance for remote treatment planning including staging discussions (44.6%) and for referral to secondary care oncologists (17.4%).ConclusionsDespite the pandemic, cancer remains the key concern and patients are not willing to compromise on their treatment. Rapid implementation of telehealth is tolerated well during the need of social distancing, with a clear "red line" concerning changes in existing patient-physician relationships. Balancing future implementation of telehealth while considering patients' demand for personal relationships will ensure human dignity in uro-oncology.Patient summaryWe queried patients with genitourinary cancers treated in an almost virtual setting following a local coronavirus outbreak. Acceptance of telehealth during the current situation is high; however, long-term implementation of the adapted services is less favored. We deduce that patient-physician relationship is crucial for cancer patients and needs to be balanced against measures for social distancing to forge the future management.

Dataset Information

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Publications

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

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