Researchers at UT Southwestern Medical Center have uncovered a key process that helps prostate cancer cells resist treatment.
Their study, published in Cancer Discovery, highlights how two genes work together to change the behavior of cancer cells, making them harder to treat.
This discovery could lead to new, more effective therapies for prostate cancer.
Prostate cancer is the most common cancer in men, with about one in eight men diagnosed in their lifetime.
A major challenge in treating advanced prostate cancer, especially metastatic castration-resistant prostate cancer (mCRPC), is its ability to develop resistance to current therapies.
This resistance often happens because cancer cells can switch their identity, a process called lineage plasticity, allowing them to evade treatments designed for their original type.
Dr. Ping Mu and his team discovered that a deficiency in a gene called Zinc Finger Protein 397 (ZNF397) triggers this identity switch in prostate cancer cells.
Normally, prostate cancer cells grow by relying on androgen receptor (AR) signaling, which current treatments target.
However, when ZNF397 is deficient, these cells shift to relying on a different gene, Ten Eleven Translocation 2 (TET2), which helps regulate DNA and its functions.
This switch makes the cancer cells more adaptable and resistant to AR-targeted therapies.
The researchers found that TET2 plays a crucial role in this process by changing the cell’s DNA structure, allowing the cancer to become more flexible and resist treatment.
Importantly, the study also showed that blocking TET2 can reverse this resistance. By inhibiting TET2, either genetically or with drugs, the researchers were able to make the cancer cells sensitive again to AR-targeted therapies, even in tumors lacking ZNF397.
This discovery builds on previous research from Dr. Mu’s lab and offers hope for new treatments.
Targeting TET2 could lead to clinical trials for patients with advanced prostate cancer, potentially improving treatment outcomes and survival rates.
Dr. Mu emphasized the potential impact of these findings, stating, “Reversing resistance by targeting TET2 with drugs opens new paths for treating patients with advanced prostate cancer.”
The researchers hope their work will lead to new therapies that can effectively combat prostate cancer’s adaptability and resistance to current treatments.
These insights mark an important step toward personalized treatment strategies, offering a new approach to managing prostate cancer and potentially improving the lives of many patients.
If you care about prostate cancer, please read studies about 5 types of bacteria linked to aggressive prostate cancer, and new strategy to treat advanced prostate cancer.
For more information about prostate cancer, please see recent studies about new way to lower risk of prostate cancer spread, and results showing three-drug combo boosts survival in metastatic prostate cancer.
