Analysis may result in higher therapy for aggressive prostate most cancers

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New research from CU Cancer Center member Scott Cramer and colleagues could help treat men with certain aggressive types of prostate cancer.

Cramer’s study, published this week in the journal Molecular Cancer Research, specifically examines how the loss of two specific genes that suppress prostate tumor – MAP3K7 and CHD1 – increases androgen receptor signaling and makes the patient more resistant to anti-androgen therapy typically given to lower testosterone levels in prostate cancer patients.

Doctors don’t usually classify patients by this subtype and say, “We need to treat these people differently.” However, we feel that this should be taken into account before they are treated with anti-androgen therapy, as they appear to be already inherently resistant to the therapy. They are less likely to respond to treatment. “

Scott Cramer, PhD, Professor, Department of Pharmacology

Cramer was the corresponding author on paper. Lauren Jillson, a PhD student in the cancer biology graduate program at Anschutz University, was the lead author of the study. Other members of the CU Cancer Center included M. Scott Lucia, MD, and James Costello, PhD. The 11 other authors were a mix of researchers from the Pharmacology Department of the CU School of Medicine and the Department of Pathology, as well as researchers from Stanford University and the University of California.

Elsewhere in the work, Cramer and his co-researchers show that loss of expression of the MAP3K7 gene in particular is linked to poor outcomes, making it even more important to treat patients who show the loss of the gene. Cramer notes that the majority of men diagnosed with prostate cancer have slow-growing tumors that are at low risk of metastasis. However, about 20% of patients eventually develop aggressive metastatic disease. Knowing that the absence of MAP3K7 and CHD1 is a signal of a more aggressive disease, and that treatments like surgery, radiation, chemotherapy, and hormone therapy can all have side effects that can be significant, Cramer hopes doctors will eventually use the deletion as one can markers for men who would benefit most from aggressive treatment strategies and who would spare those who are less likely to succumb to their disease.

“These patients should be treated more aggressively than other patients because they are more likely to die from the disease,” he says. “And we know that 50% of patients with loss of MAP3K7 and CHD1 are likely to come back after their initial treatment for relapsing diseases.”

A previous study by Cramer showed that in prostate cancer patients with combined MAP3K7 and CHD1 deletions, about half had recurrent prostate cancer, ultimately leading to death. About 10-15% of all prostate cancers have combined MAP3K7-CHD1 deletions. He and his team are currently investigating alternative treatments for patients who are resistant to anti-androgen therapy because of the deletions.

“Our ultimate goal is better treatment,” he says. “There is a lot more work to be done to reproduce our results, validate them, and then expand them to preclinical models. If all of them look good, patients could potentially be stratified based on their expression of these proteins, and then hopefully we have better options to treat them. “

Source:

University of Colorado Anschutz Medical Campus

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