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Glactone Pharma: STAT3 interacts with the androgen receptor and is a drug target in enzalutamide resistant prostate cancer

27 November, 2018

In collaboration with researchers at Vancouver Prostate Centre in Canada, Glactone Pharma has discovered a novel way of enhancing the effects of current prostate cancer treatments. The research, published in the scientific journal Scientific Reports, demonstrates that STAT3 inhibition could be a part of a combination therapy together with anti-androgens against castration resistant prostate cancer thereby offering new treatment options for prostate cancer patients.

Prostate cancer is the most common form of non-cutaneous cancer in men. The yearly incidence in the seven largest markets is over 400,000 men and the number of patients exceeds 1,6 million. In many cases the disease progresses to a state were androgen deprivation no longer has any effect, so called castration resistant prostate cancer (CRPC). However, primary and acquired resistance to current drugs is a very large clinical problem and treatments that either reverse or prevent resistance would have a great impact on the treatment of prostate cancer. Metastatic CRPC is almost always incurable.

Glactone Pharma is a Swedish biotech company developing novel drugs that can inhibit the transcription factor STAT3, a highly relevant drug target in cancer, including prostate cancer. Using the natural product galiellalactone as a starting point, Glactone Pharma has built a unique and promising portfolio of STAT3 inhibitors with excellent druglike properties that can address unmet medical needs. Together with the company’s innovators at Lund University and other academic collaborators, Glactone Pharma has built a strong scientific case that STAT3 is an important target in prostate cancer.

Together with a research group at the Vancouver Prostate Centre in Canada, it has now been shown that STAT3 can interact with the androgen receptor (AR) and enhance the AR signaling that drives prostate cancer. Furthermore, treating prostate cancer cells with a clinically used anti-androgen drug, enzalutamide, resulted in STAT3 activation. Finally, enzalutamide resistant prostate cancer cells became sensitive to STAT3 inhibition using the natural product galiellalactone. In conclusion the results show that targeting STAT3 has the potential to stop or reverse treatment resistance, prevent disease progression and enhance the effect of current drugs used in prostate cancer. The results have been published as an article, “Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer”, in Scientific Reports, a scientific journal from the publishers of Nature.

Martin Johansson, CEO of Glactone Pharma, says: “Based on these new findings, we believe we can address a great unmet medical need and potentially bring forward innovative and effective treatment options for prostate cancer patients. We are very grateful for this productive collaboration with the Vancouver Prostate Centre.”

About STAT3
STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor/signaling protein that is frequently activated in many forms of cancer.

STAT3 is a highly promising target in cancer with both preclinical and clinical data supporting the important roles that STAT3 plays in cancer occurrence and progression. In particular, STAT3 is involved in mechanisms that enable tumors and cancer cells to escape the immune system and also become treatment resistant.

STAT3 is an intractable drug target as it is an intracellular protein with no enzymatic activity and is activated by multiple upstream factors. Despite STAT3 not being a “classic drug target”, Glactone Pharma has developed orally bioavailable small molecule inhibitors that can directly inhibit the function of STAT3.

Link to the on-line article “Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer”:
https://www.nature.com/articles/s41598-018-35612-z.

About Glactone Pharma
Glactone Pharma is a biotech company within PULS and is based on ground-breaking science from Lund University in Sweden. PULS is a Swedish life science company with a unique combination of scientists and industrialists who together with innovators are commercializing ideas by providing capital, know-how and committed partnership.
Glactone Pharma has developed a pipeline of novel potential drugs that target the STAT3 transcription factor for the use in immuno-oncology and for the treatment of advanced treatment resistant cancers. STAT3 is directly involved in tumor mediated immune suppression and in treatment resistance making it an ideal target in combination treatments.
To read more, visit www.glactone.com and www.pulsinvest.se.

For more information, please contact
Jan Törnell, Chairman of the Board, Glactone Pharma AB, +46 (0)70 676 00 08 or jan.tornell@pulsinvest.se
Martin Johansson, CEO, Glactone Pharma AB, +46 (0)76 006 60 29 or martin.johansson@glactone.com

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