Genetic Testing at Prostate Cancer Diagnosis and Monitoring May Lead to Better Treatments

Genetic Testing at Prostate Cancer Diagnosis and Monitoring May Lead to Better Treatments

Patients with prostate cancer should be monitored for genetic changes not only at the time of diagnosis but also during treatment as the disease progresses, according to Prof. Tapio Visakorpi from the University of Tampere in Finland. Knowing the genetic landscape of patients will lead to more tailored treatments, ultimately improving patient’s outcomes, he said.

“Most of the prostate cancers diagnosed are relatively benign and don’t necessarily require active treatment. On the other hand, some prostate cancers are highly aggressive. A major problem from the treatment perspective is that once the disease has been diagnosed, the clinical course is difficult to predict reliably,” Visakorpi said in a press release.

Understanding the underlying mechanisms of prostate cancer in individual patients is necessary to identify which treatment is more likely to work. Visakorpi, who is studying the molecular biology of prostate cancer with funding by the Academy of Finland, is aiming to improve the knowledge we already have on potential targets for prostate cancer treatment and has been trying to improve the method that is currently employed to examine tumor samples.

“Recent genome studies have shown that even though prostate cancer initiates in a single cell of origin, several cancer cell subpopulations with different genome types emerge as the disease progresses. This is not a single disease; several mechanisms lead to the emergence of the disease,” he said. “Therefore, it’s important to identify those genome defects in each patient that occur in all cancer cells — that is, the so-called truncal mutations, and target the treatment to them.”

“This requires taking multiple samples from the patient. The processing of samples also needs to be improved to make them more suitable for molecular analysis than the current methods. We’ve developed a new processing method for cancerous tissue,” Visakorpi added.

But Visakorpi also notes that patients should not only be tested as they are diagnosed but also when the disease progressed following a given treatment. This is supported by findings that tumors can become resistant to certain therapies through the acquisition of certain mutations that counteract the inhibitory effect of the drugs.

One example is the resistance to androgen deprivation therapies, a gold standard in the treatment of prostate cancer. Because prostate cancer cells rely on male hormones, called androgens, for growth, inhibiting the production of such hormones or their interaction with their specific receptor is a common approach in prostate cancer treatment.

But as the cancer evolves, the cancer cells acquire mutations that allow them to activate the androgen signaling pathway without requiring the androgens to bind to the receptors. At this point, patients have what is commonly known as castration-resistant prostate cancer.

“It was already proven back in the 1990s that one mechanism stimulating this reactivation is the amplification of the androgen receptor (AR) gene. New research has shown that glucocorticoid medication, which is often used to treat end-stage prostate cancer, can turn against the patient. This causes a mutation in the AR gene, which leads to the activation of the signalling pathway by glucocorticoids,” Visakorpi said.

But to understand which treatment is more likely to exert an effect in these patients, doctors need to know which mutations they have acquired in the course of their prior treatment.

“All this indicates that we should be able to monitor the genome changes in each patient’s cancer cells, not just at the time of diagnosis but also during treatment as the disease progresses,” Visakorpi said. “This would allow for the tailoring of the cancer therapy at any given time throughout the progression of the disease.”

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Inês Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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