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The aim of this study is to use multiomics sequencing to explore the molecular characteristics of metastatic prostate cancer (mPCa), especially metastatic castration-resistant prostate cancer (mCRPC). At the same time, mCRPC models will be constructed, including organoids and animal models, serving as a basic and translational research platform to help identify novel drug targets for mPCa.
Although substantial progress in treatments for prostate cancer have been made in the past decades, distant metastasis and drug resistance remained a major cause of prostate cancer-related deaths. The five-year survival rate for men with mPCa was only 30% and all patients with mPCa would inevitably progress to the castration-resistant stage with limited therapeutic chance. In China, the current situation is more worrying, with rapidly increasing PCa incidence and higher proportion of mPCa diagnosed compared with the Western nations (~30% vs ~5%).
Multiomics sequencing provides a promising strategy to discover the underlying molecular basis driving metastasis and resistance and identify the new treatment strategies for patients with mCRPC. The candidate drug target revealed by the multiomics sequencing could be further examined in the organoid and animal models, facilitating the clinical application from basic discovery.
This study can establish a mCRPC research system to find the molecular mechanism and potential intervention targets of mCRPC, thereby paving the way for the discovery of new treatments for mCRPC patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All patients | There is only one arm in the trial |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tissue | Other | Tissue will be derived from patients during a standard of care procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| Multiple omics features | Multi-omics information including genetic profiling results, transcriptional profiling results and epigenomic profiling results will be collected and analyzed. | 3 years |
| Organoids successfully generated from metastatic prostate cancer | Successful isolation of prostate cancer organoids from surgical specimens of patients diagnosed with metastatic prostate cancer. We will calculate the culture efficiency and total number of organoids generated in our center. | 3 years |
| Developing of biomarkers related to cancer metastasis and drug resistant | To search for biomarkers related to tumor metastasis and resistance by performing multi-omics analysis to surgery specimens derived from patients with metastatic prostate cancer. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Animal models successfully generated from patient derived prostate cancer organoids | Prostate cancer organoids with clarified characteristics will be transplanted into mice to establish PDOX models. | 3 years |
| Response of the prostate cancer organoids to the selected anti-cancer compounds |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with metastatic prostate cancer especially metastatic castration resistant prostate cancer will be recruited for this study.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yao Zhu | Contact | +86 15001818005 | mailzhuyao@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36055231 | Background | Akhoundova D, Rubin MA. Clinical application of advanced multi-omics tumor profiling: Shaping precision oncology of the future. Cancer Cell. 2022 Sep 12;40(9):920-938. doi: 10.1016/j.ccell.2022.08.011. Epub 2022 Sep 1. | |
| 35986012 | Background | Yerly L, Pich-Bavastro C, Di Domizio J, Wyss T, Tissot-Renaud S, Cangkrama M, Gilliet M, Werner S, Kuonen F. Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma. Nat Commun. 2022 Aug 20;13(1):4897. doi: 10.1038/s41467-022-32670-w. |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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Not provided
| ID | Term |
|---|---|
| D006650 | Histocompatibility Testing |
| ID | Term |
|---|---|
| D007159 | Immunologic Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Organoid that are successfully cultured and characteristic clarified will be treated with the selected compounds to test their anti-cancer activity. |
| 3 years |
| Response of the PDOX models to the selected anti-cancer compounds | PDOX models that successfully established will be treated with the selected compounds to test their anti-cancer activity. | 3 years |
| 33692499 | Background | Zhu Y, Mo M, Wei Y, Wu J, Pan J, Freedland SJ, Zheng Y, Ye D. Epidemiology and genomics of prostate cancer in Asian men. Nat Rev Urol. 2021 May;18(5):282-301. doi: 10.1038/s41585-021-00442-8. Epub 2021 Mar 10. |
| 31248605 | Background | Wei Y, Wu J, Gu W, Qin X, Dai B, Lin G, Gan H, Freedland SJ, Zhu Y, Ye D. Germline DNA Repair Gene Mutation Landscape in Chinese Prostate Cancer Patients. Eur Urol. 2019 Sep;76(3):280-283. doi: 10.1016/j.eururo.2019.06.004. Epub 2019 Jun 24. |
| 25201530 | Background | Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, Wongvipat J, Kossai M, Ramazanoglu S, Barboza LP, Di W, Cao Z, Zhang QF, Sirota I, Ran L, MacDonald TY, Beltran H, Mosquera JM, Touijer KA, Scardino PT, Laudone VP, Curtis KR, Rathkopf DE, Morris MJ, Danila DC, Slovin SF, Solomon SB, Eastham JA, Chi P, Carver B, Rubin MA, Scher HI, Clevers H, Sawyers CL, Chen Y. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014 Sep 25;159(1):176-187. doi: 10.1016/j.cell.2014.08.016. Epub 2014 Sep 4. |
| 36114082 | Background | Guo C, Figueiredo I, Gurel B, Neeb A, Seed G, Crespo M, Carreira S, Rekowski J, Buroni L, Welti J, Bogdan D, Gallagher L, Sharp A, Fenor de la Maza MD, Rescigno P, Westaby D, Chandran K, Riisnaes R, Ferreira A, Miranda S, Cali B, Alimonti A, Bressan S, Nguyen AHT, Shen MM, Hawley JE, Obradovic A, Drake CG, Bertan C, Baker C, Tunariu N, Yuan W, de Bono JS. B7-H3 as a Therapeutic Target in Advanced Prostate Cancer. Eur Urol. 2023 Mar;83(3):224-238. doi: 10.1016/j.eururo.2022.09.004. Epub 2022 Sep 13. |
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D008919 | Investigative Techniques |
| D007158 | Immunologic Techniques |