Patients helping researchers to advance treatments for prostate cancer

Patients helping researchers to advance treatments for prostate cancer
Pathological and clinical features of tumors used to establish PDXs. a Pie charts show the number of patients consented and the number of primary prostate tumor samples collected for xenografting compared to the number of samples that maintained tumor tissue in the first generation (G1) PDX and established as serially transplantable (ST) PDXs. Color denotes the site that each sample was taken from. b–d The percentage of Ki67-positive tumor cells in pre-grafted tissue (b; n = 14 ST, 38 non ST), time to first generation (c; n = 14 ST, 49 non ST), and tumor volume at surgery for radical prostatectomy (RP; orange) and transurethral resection of the prostate (TURP; purple) specimens (d; n = 13 ST, 28 non ST, P = 0.016) that established ST PDXs compared to those that did not. Unpaired two-sided T test for ST vs non ST; data shown as mean ± SEM. e The percent of primary tumors with a Gleason grade group of 1–5 that did (n = 13) or did not establish ST PDXs (n = 30; not significant, Mann Whitney test comparing the distribution of Gleason grade groups between ST vs non ST). f Kaplan–Meier curve comparing the survival of patients whose RP specimen did (orange; n = 13) or did not (blue; n = 37) establish ST PDXs. P = 0.0072; log rank test; HR = 10.93; 95% CI 1.51 to 79.08. g Pie charts show the number of patients consented and the number of metastatic tumor samples collected for xenografting compared to the number of samples that maintained tumor tissue in the G1 PDX and established as serially transplantable PDXs. Color denotes the site that each sample was taken from. h–i The percentage of Ki67-positive tumor cells in pre-grafted tissue (h; n = 25 ST, 94 non ST, P < 0.0001), and time to first generation (i; n = 28 ST, 117 non ST, P <  0.0001) for metastatic tumor samples obtained from surgery/biopsy (yellow) or autopsy (purple) that did or did not establish ST PDXs. Unpaired two-sided T test for ST vs non ST; data shown as mean ± SEM. j The percentage of androgen receptor (AR)-positive and AR-negative metastatic tumors that did (n = 25) or did not establish ST PDXs (n = 80), based on immunohistochemistry for AR in the original tumor tissue. Not significant; Fisher’s exact test. Source data are provided as a Source Data file. Credit: DOI: 10.1038/s41467-021-25175-5

Researchers at Monash University have established one of the world's largest collections of living tumors from prostate cancer patients, accelerating the testing of new treatments for prostate cancer and leading to faster patient benefit.

One of the most common cancers, prostate is also one of the most difficult to study in the laboratory, with the frequently used models derived more than 40 years ago. With the establishment of the Melbourne Urological Research Alliance (MURAL), hundreds of Victorian men have generously donated samples of their cancer tissue, enabling the team to study a greater diversity of live tumors and test the efficacy of a larger variety of therapies for their ability to stop tumor growth.

The PDX collection (patient-derived xenografts), developed by a multidisciplinary consortium and led by Professor Gail Risbridger and Associate Professor Renea Taylor at the Monash Biomedicine Discovery Institute (BDI), now comprises 59 tumors, collected from 30 patients between 2012—2020 and is now one of the largest collections of prostate cancer models in the world.

Full characterisation of the PDX collection is published in Nature Communications.

MURAL PDXs are an enduring resource of new cancer models that can be shared with other academic investigators or pharmaceutical companies. The patients and their families are directly embedded in this venture, including the EJ Whitten Foundation who have been pivotal over the last 10 years in providing over $1M in donations enabling this resource to be developed and the program to come to the forefront of the international field.

"This project begins and ends with patients like EJ Whitten. We take patient tissue—do testing in the laboratory—and the discoveries then advance treatment for patients," said Professor Risbridger. "Our new models of prostate cancer have attracted interest from scientists and the pharmaceutical industry worldwide."

Ted Whitten, and founder of the E.J.Whitten Foundation congratulates the Monash University Biomedicine Discovery Institute on its recent findings in regards to Prostate Cancer research. "We believe that Monash University is a leader of Prostate Cancer Research and we have been delighted to have been able to financially support many of their important programs over the past ten years."

Dr. Mitchell Lawrence, also from Monash BDI and a senior author, says: "This resource provides an opportunity to link the molecular changes in cancer to pathology, grow organoids and test functional responses to therapies, which have rarely been applied to given the lack of suitable models."


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More information: Gail P. Risbridger et al, The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology, Nature Communications (2021). DOI: 10.1038/s41467-021-25175-5
Journal information: Nature Communications

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