Scientists at Weill Cornell Medicine discovered that the enzyme EZH2 drives aggressive, treatment-resistant prostate cancer when a protein called PKCλ/ι is absent. This alternative EZH2 activity fosters tumour growth despite androgen receptor therapies. Blocking EZH2 or TGF-β pathways reversed resistance in preclinical studies, offering new hope for tailored treatments to combat this challenging cancer type.
New Target Found for Treatment-Resistant Prostate Cancer: A groundbreaking study by scientists at Weill Cornell Medicine has uncovered a surprising role for the enzyme EZH2 in driving the growth of treatment-resistant prostate cancer. This discovery could pave the way for innovative therapies to tackle one of the deadliest forms of prostate cancer, neuroendocrine prostate cancer, which no longer responds to standard treatments.
Published on November 20 in Nature Communications, the research led by Drs. Maria Diaz-Meco and Jorge Moscat offer new hope for patients battling advanced prostate cancer with limited treatment options. The findings highlight a previously unknown mechanism that allows cancer cells to bypass androgen receptor inhibitors, the cornerstone of current prostate cancer therapy.
Also Read: Johns Hopkins Study Highlights Bats' innate ability to navigate without sound
Prostate cancer is the second leading cause of cancer-related deaths among men in the United States, claiming over 30,000 lives annually. While many cases respond to initial treatment with androgen receptor inhibitors, some tumours evolve into a more aggressive and treatment-resistant form called neuroendocrine prostate cancer. Unlike typical prostate cancers, these tumours no longer depend on androgen signalling for growth, making them incredibly difficult to treat.
Understanding how prostate cancer transitions to this resistant form has become a top priority for researchers and clinicians. The new study provides a key piece of this puzzle by identifying how EZH2, an enzyme known for regulating genes, contributes to aggressive tumour growth in this setting.
The study revealed that EZH2 plays a different role in prostate cancer cells lacking a protein called PKCλ/ι. Normally, PKCλ/ι suppresses EZH2’s activity, ensuring it doesn’t promote tumour growth. However, when PKCλ/ι is absent—a common occurrence in advanced prostate cancer—EZH2 adopts an alternative function.
Instead of repressing tumor-suppressor genes, this new form of EZH2 drives the production of proteins and activates growth factors like TGF-β. These changes create an environment that fosters tumour progression, even in the presence of androgen receptor inhibitors like enzalutamide.
“This study reveals a critical mechanism behind treatment resistance in prostate cancer, suggesting new therapeutic approaches,” said Dr. Diaz-Meco, a professor of oncology at Weill Cornell Medicine.
To explore possible treatments, the research team conducted preclinical studies targeting EZH2’s alternative activities. They found that blocking either protein production or the TGF-β pathway reversed resistance in cancer cells lacking PKCλ/ι.
By inhibiting EZH2’s alternative function, the researchers restored the cancer’s sensitivity to androgen receptor inhibitors. This breakthrough suggests that combining EZH2 inhibitors with existing therapies could provide a powerful new strategy for treating resistant prostate cancers.
Additionally, since TGF-β suppresses the immune system in tumours, targeting this pathway may also enhance the effectiveness of immunotherapies, which have shown limited success against prostate cancer alone.
While the findings are promising, the researchers emphasized the need for personalized approaches. The absence of PKCλ/ι creates a specific vulnerability in cancer cells, making them particularly susceptible to combined treatments targeting EZH2 and TGF-β.
However, the study also found that inhibiting EZH2 in tumours with normal PKCλ/ι levels can counteract the benefits of therapy, underscoring the importance of tailoring treatments to each patient’s unique tumour biology.
“Achieving a careful balance is essential to avoid reversing treatment benefits,” said Dr. Moscat, a professor of oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
The research lays the foundation for clinical trials combining androgen receptor inhibitors with EZH2 or TGF-β inhibitors. Such trials could provide a much-needed lifeline for patients with therapy-resistant prostate cancer.
“This work not only sheds light on how advanced prostate cancer develops resistance but also highlights new ways to potentially re-sensitize tumours to treatment,” said Dr. Diaz-Meco.
The findings may also have broader implications for other types of cancer, as the mechanisms involving EZH2 and PKCλ/ι could play similar roles in different tumour types.
The study reflects years of collaborative work by leading scientists. Co-first authors include Dr. Shankha Chatterjee, Dr. Juan Linares, Dr. Tania Cid-Diaz, and Dr. Angeles Duran, all members of the Moscat and Diaz-Meco laboratories.
Grants from the National Cancer Institute and the National Institute of General Medical Sciences, part of the National Institutes of Health, supported the research.
This discovery marks an important step in understanding and combating treatment-resistant prostate cancer. By uncovering the role of EZH2 and its interaction with PKCλ/ι, researchers have opened the door to new therapeutic strategies.
As clinical trials advance, the hope is that these findings will lead to more effective treatments, giving patients battling aggressive prostate cancer a better chance at survival.
“By understanding EZH2’s role in this context, we may be able to create more precise and effective therapies, making cancer newly vulnerable to targeted treatments,” Dr. Diaz-Meco said.
This research underscores the power of precision medicine and highlights the importance of tailoring treatments to individual patients for better outcomes. Keep reading Education Post News for ongoing global updates.
Loading ...
Copyright© educationpost.in 2024 All Rights Reserved.
Designed and Developed by @Pyndertech