Hard-to-detect prostate cancer may grow through cancer-stroma KRAS signaling
· Medical Xpressedited by Sadie Harley, reviewed by Andrew Zinin
Sadie Harley
Scientific Editor
Meet our editorial team
Behind our editorial process
Andrew Zinin
Lead Editor
Meet our editorial team
Behind our editorial process Editors' notes
This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
fact-checked
trusted source
proofread
The GIST Add as preferred source
A research team at Kanazawa University, led by Professor Atsushi Mizokami, Associate Professor Koji Izumi and Specially Appointed Assistant Professor Taiki Kamishima (a fourth-year doctoral student at the Graduate School of Medical Sciences), has elucidated a novel molecular mechanism driving the progression of "double-negative castration-resistant prostate cancer (DNPC)"—one of the most treatment-resistant forms of prostate cancer.
In recent years, the widespread use of potent, novel androgen receptor-targeted therapies has led to a rapid surge in DNPC cases. DNPC poses a critical clinical challenge because it progresses and metastasizes without causing elevations in conventional tumor markers such as prostate-specific antigen (PSA) or neuroendocrine markers (NSE, ProGRP), making it difficult to detect via routine blood tests.
Consequently, DNPC represents a severe and growing threat in clinical oncology, with no established effective therapies.
A study published in the journal Cell Death & Disease
reveals that when androgen receptor (AR) signaling is intensively suppressed by hormone therapy, a vicious reciprocal interaction is triggered between prostate cancer cells and the surrounding prostate stromal cells (fibroblasts).
Specifically, cancer cell-derived CCL2 stimulates stromal cells to secrete FGF8b, which in turn aberrantly activates the KRAS oncogene pathway in cancer cells. This cancer-stromal interaction allows the cancer cells to evade apoptosis (programmed cell death) and continue growing.
The research team demonstrated that a pan-KRAS inhibitor successfully suppressed the proliferation, migration and invasion of prostate cancer cell lines exhibiting DNPC characteristics, effectively inducing apoptosis. These findings are expected to pave the way for the development of novel therapeutic strategies for DNPC patients who currently face limited options.
"Double-negative prostate cancer (DNPC) has recently emerged as a daunting clinical challenge due to its stealthy progression and lack of effective treatments," the research team noted.
"Focusing on prostate stromal cells and capturing the precise, dynamic interactions between them and prostate cancer cells was an experimentally challenging and arduous process. However, by overcoming these hurdles, we were able to identify the exact mechanism of KRAS signaling activation within the prostate microenvironment—a setting that much more closely mimics actual clinical conditions. This discovery opens up an entirely new dimension for therapeutic intervention."
With the global landscape of KRAS inhibitors advancing at an unprecedented pace, the research group next aims to further evaluate these laboratory findings using other cutting-edge agents. "Our next step is to validate the efficacy of the latest advanced KRAS-targeted agents," the investigators added.
"Ultimately, we envision exploring synergistic combination therapies that pair KRAS inhibitors with FGFR or beta-catenin inhibitors. By directly disrupting the vital communication between cancer cells and the prostate stroma, this approach has the potential to establish a completely paradigm-shifting therapeutic strategy for intractable DNPC."
More information
Taiki Kamijima et al, Fibroblast-mediated KRAS activation in double-negative prostate cancer, Cell Death & Disease (2026). DOI: 10.1038/s41419-026-08800-3
Key medical concepts
Clinical categories
OncologyUrology Provided by Kanazawa University Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
Andrew Zinin
Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →
Citation: Hard-to-detect prostate cancer may grow through cancer-stroma KRAS signaling (2026, June 12) retrieved 12 June 2026 from https://medicalxpress.com/news/2026-06-hard-prostate-cancer-stroma-kras.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.