Nat Commun: The response of transplanted tumors and organoid models from prostate cancer patients to treatment

Prostate cancer (PCa) is the second most commonly diagnosed type of cancer and the fifth leading cause of cancer-related death among men worldwide .
Due to the hormone sensitivity of the prostate, androgen deprivation therapy is currently used to prevent tumor growth.
However, some cancer patients develop resistance and develop castration-resistant prostate cancer (CRPC).

Prostate cancer (PCa) is the second most commonly diagnosed type of cancer and the fifth leading cause of cancer-related death among men worldwide .
Prostate cancer (PCa) is the second most commonly diagnosed type of cancer and the fifth leading cause of cancer-related death among men worldwide .
diagnosis

New androgen inhibitors, such as enzalutamide and abiraterone, have now been used in the treatment of CRPC.
However, acquisition of drug resistance and intratumoral heterogeneity limit their efficacy.
Therefore, the use of drugs with different mechanisms of action is forced.
The lack of early-stage experimental models of early-stage PCa that can be used for treatment is the main limitation of pre-clinical PCa research.

The lack of early-stage experimental models of early-stage PCa that can be used for treatment is the main limitation of pre-clinical PCa research.
The lack of early-stage experimental models of early-stage PCa that can be used for treatment is the main limitation of pre-clinical PCa research.

Due to the lack of experimental models that can simulate different disease stages, the treatment resistance of PCa and the process of disease metastasis are still unclear.

Establishment of transplanted tumor model

In this study, the researchers constructed an in situ treated soft tissue metastasis (PNPCa) androgen-dependent PCa patient-derived xenograft tumor (PDX) model.

Through RNA and whole-exome sequencing of PDX tissues and organoids, the researchers confirmed the similarity between the model and the transcriptome and genome of the primary tumor.

Studies have shown that PNPCa has somatic mutations in the BRCA2 and CHD1 genes, exhibits SPOP/FOXA1-like transcriptomic characteristics and microsatellite instability.

This situation only occurs in 3% of patients with advanced PCa, and has not been performed in Body modeling.

Correlation between genomic characteristics and specific drug response in organoid models

Multi-kinase inhibitors (ponatinib, sunitinib, sunitinib, sorafenib) have a wide range of effects on all PDX models and organoids derived from advanced patients who are resistant to standard compounds of treatment.

Sunitinib

All in all, this proof-of-principle study may provide a preclinical tool to screen relevant patient care standard drugs and identify novel compounds.

This proof-of-principle study may provide a preclinical tool to screen relevant patient care standard drugs and identify novel compounds.

This proof-of-principle study may provide a preclinical tool to screen relevant patient care standard drugs and identify novel compounds.

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