Roswell Park Researchers Identify New Treatment Target for Prostate Cancer

22/06/2022, 12:11 https://www.pressreleasepoint.com/print/1949451
Roswell Park Researchers Identify New Treatment
Target for Prostate Cancer
Posted June 16th, 2022 by rahulitrc
Components of mitochondrial stress response could be key to overcoming resistant/recurrent
prostate cancer
Buffalo, New York, USA., June 16, 2022 - /PressReleasePoint/ — A team of researchers at Roswell
Park Comprehensive Cancer Center, led by Dhyan Chandra, PhD , have uncovered evidence that could
lead to the development of a new treatment option for patients with metastatic, resistant or recurrent
prostate cancer. Their findings, published today in the Journal of Clinical Investigation , suggest that
mitochondrial unfolded protein response — a unique longevity function of mitochondria — could be a
new target for the treatment and management of this patient population.
The standard first-line approach for prostate cancer typically targets the main driver of the disease —
the androgen receptor signaling axis. While current therapeutic agents initially reduce tumor burden,
disease recurrence is likely and, for patients with a hormone-resistant phenotype, drugs that target the
androgen receptor are ineffective.
“Patients with hormone-refractive prostate cancer are typically treated with taxanes such as docetaxel
or cabazitaxel, but outcomes are overwhelmingly poor in those with advanced disease, nearly all of
whom will see their cancer return following initial treatment,” says Dr. Chandra, Associate Professor of
Oncology in the Department of Pharmacology & Therapeutics at Roswell Park. “There is an urgent
need to identify and develop treatment modalities for prostate cancer that do not rely on targeting the
androgen receptor signaling axis.”
Dr. Chandra and his team found that two key components of the mitochondrial unfolded protein
response (UPRmt) were necessary for the development of advanced prostate cancer. These included the
heat shock protein 60 (HSP60), a mitochondrial chaperonin, and caseinolytic protease (ClpP), a
mitochondrial protease.
“The HSP60-mediated chaperonin system facilitates protein folding, whereas ClpP protease degrades
unfolded protein to maintain mitochondrial protein homeostasis, which is critically required for cancer
cell survival and growth,” explains Dr. Chandra, while noting that HSP60 acts as upstream regulator of
ClpP and HSP60 interacts with ClpP. “This suggests that a drug that interferes with the interaction of
HSP60 and ClpP will disrupt cancer cell survival and block the growth and progression of prostate
cancer.”
The researchers also identified a novel mitochondrial unfolded protein response inhibitor, DCEM1, that
hampers HSP60’s interactions with ClpP in prostate cancer cells and tumors. In their preclinical studies,
the authors show that this inhibition of HSP60-ClpP interaction impeded the development of resistant
or aggressive disease. The study’s first author, Rahul Kumar, PhD , Research Associate at Roswell
Park, discovered that using DCEM1 to disrupt the interactions between HSP60 and ClpP interferes with
survival signaling and triggers metabolic stress, which results in the death of prostate cancer cells.
The team demonstrates that targeting the HSP60-ClpP axis — which is unregulated in prostate cancer
irrespective of androgen receptor status — is a promising therapeutic approach for this patient
population.
“This study provides strong evidence for developing a novel drug for the treatment of metastatic and
resistant prostate cancer,” notes Dr. Chandra. “Since the current androgen deprivation and taxane-based
therapies are not effective, these findings provide alternative treatment approaches for prostate cancer
that do not rely on androgen receptor signaling axis.”
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22/06/2022, 12:11 https://www.pressreleasepoint.com/print/1949451
This work was funded by grants from the National Cancer Institute (R01CA160685, R01CA246437,
R01CA207757, R01CA234162, R01CA237027, R01CA240290 and P30CA016056) and American
Cancer Society (MBG-21- 048-01-MBG and RSG-12-214-01–CCG), with additional support from
donations to Roswell Park.
About Roswell Park
Roswell Park Comprehensive Cancer Center is a community united by the drive to eliminate cancer’s
grip on humanity by unlocking its secrets through personalized approaches and unleashing the healing
power of hope. Founded by Dr. Roswell Park in 1898, it is the only National Cancer Institutedesignated
comprehensive cancer center in Upstate New York. Learn more at www.roswellpark.org, or
contact us at 1-800-ROSWELL (1-800-767-9355) or ASKRoswell@RoswellPark.org .
Press Contact:
Annie Deck-Miller
Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets,Buffalo, NY 14263
716-845-8593
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