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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 |

REPOSITORIES: biostudies-literature

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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.

Project description:OBJECTIVE:To evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore. DESIGN:Retrospective analysis of a large prospective Uro-oncology registry of mPCa. SETTING:This study is carried out in a tertiary hospital in Singapore. PARTICIPANTS:We reviewed our institution's prospectively maintained database of 685 patients with mPCa over a 20-year period (1995-2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES:The primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years. RESULTS:237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50?g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7-27). The median overall survival was 45 months (IQR 20-63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995-1999) to 47.8 months (2010-2014) (p<0.01). CONCLUSION:Morbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

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

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