Prostate Cancer dormancy – recent Australian study. “Prostate cancer cell‐intrinsic interferon signaling regulates dormancy and metastatic

[Bjry]

You need more molecular cell biology than I have to follow the detail of this long complex research study. A significant element for me was that they tested their mouse study findings against actual Pca patient samples. Hopefully this study will lead to clinical trials.

“Abstract.

The latency associated with bone metastasis emergence in castrate‐resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single‐cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor‐intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor‐intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor‐intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long‐term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor‐intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone‐metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune‐based therapies in solid cancers.”

A later quote:

“The unequivocal link between IFN signaling and bone metastasis identified in the murine CRPC model led us to investigate the importance of type I IFN alterations in PCa patients, given the current lack of patient responses to conventional and immune‐targeting therapies in bone‐metastatic CRPC. To address this, we compared the transcriptional profiles of bone metastases (n = 9) and matched primary tumors (n = 12) from a cohort of PCa patients. Hierarchical clustering revealed high similarity in gene expression patterns within both the primary tumor and bone metastases groups.”

The full details are at:

embopress.org/doi/10.15252/...

[Medline]

A new study shows that stimulation of androgen receptor-expressing prostate cancer cells by Methyltestosterone (and to a lesser extent DHT) enhances type I IFN signaling through activation of cellular responses similar to those induced by exogenous virus infection.

Results

-- Methyltestosterone is a potent stimulator of androgen receptor activity and suppressor of prostate cancer cell growth

-- Methyltestosterone suppresses DNA replication and repair pathways in prostate cancer cells

-- Methyltestosterone causes DNA hypomethylation in prostate cancer cells

-- Methyltestosterone induces transcription of transposable elements and causes accumulation of double-stranded RNA

-- Methyltestosterone activates IFN signaling

-- Methyltestosterone can enhance the interaction between prostate cancer cells and T cells

aacrjournals.org/cancerresc...