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The status of prostate cancer cells depends on the activity of the transcription factor androgen receptor (AR), which is the main therapeutic target for primary and advanced disease.
The current treatment strategy for metastatic castration-resistant prostate cancer (mCRPC) is the second-generation androgen-targeted therapy, including enzalutamide and abiraterone.
The current treatment strategy for metastatic castration-resistant prostate cancer (mCRPC) is the second-generation androgen-targeted therapy, including enzalutamide and abiraterone.
mCRPC is usually fatal and exhibits inherent or acquired resistance to second-generation androgen-targeted therapies, with minimal response to immune checkpoint inhibitors.
However, the relevant cellular processes that drive drug resistance in cancer and immune cells are still poorly understood.
In this study, the researchers analyzed single-cell transcriptome data from 14 patients with advanced prostate cancer covering all common metastatic sites (bone, lymph nodes, and liver).
The results showed that regardless of therapeutic exposure, cancer cells generally co-express multiple androgen receptor subtype proteins, including truncated proteins that are thought to mediate resistance to androgen-targeted therapy.
Multiple AR subtypes are commonly co-expressed in different disease stages and drug resistance states
Researchers found that the resistance of enzalutamide is related to the inherent epithelial-mesenchymal transition (EMT) process of cancer cells and the TGF-β signal transduction pathway.
Small cell cancer cells show different expression programs, which are driven by HOXB5, HOXB6, and NR1D2, as well as transcriptional regulators that promote plasticity.
In addition, some patients have high expression of dysfunction-related markers in the cloned cytotoxic CD8+ T cells after enzalutamide treatment.
Up-regulation of EMT and TGF-β related signals in adenocarcinoma cells treated with enzalutamide
All in all, the results of this study reveal the cancer and immunological characteristics of metastatic castration-resistant prostate cancer.
These findings also provide a theoretical basis for the development of related treatment strategies for the disease.
These findings also provide a theoretical basis for the development of related treatment strategies for the disease.
The results of this study reveal the cancer and immunological characteristics of metastatic castration-resistant prostate cancer.
These findings also provide a theoretical basis for the development of related treatment strategies for the disease.
Original source:
He, MX, Cuoco, MS, Crowdis, J.
et al.
org/10.
org/10.
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