Meet the Investigator: Dr. Massimo Loda

As a well respected researcher in the field of prostate cancer, Massimo Loda, M.D. has been a Prostate Cancer Foundation-sponsored investigator for nearly two decades. With those years of work to draw upon, his investigations today have linked a specific enzyme to the development of prostate cancer.

The enzyme in question, termed fatty acid synthase (FASN), is an enzyme involved in lipid metabolism that has been shown to be overexpressed in the majority of prostate cancer samples studied in Dr. Loda’s Boston-based research laboratory.

“We still lack biomarkers and therapeutic targets in prostate cancer, but the discovery of fatty acid synthase now represents a step forward in the right direction,” said Dr. Loda, Director of the Center of Molecular Oncologic Pathology at Dana-Farber Cancer Institute. “We hope to bring these results back to the clinic, so we can use them to help prostate cancer patients.”

Continued studies in this area by Dr. Loda and his group could lead to the discovery of inhibitors which will block the FASN gene’s ability to sustain prostate carcinogenesis.

A New Frontier
Until recently, metabolic enzymes were not thought to have much (if any) role in prostate cancer progression. Dr. Loda's team is specifically focusing on the FASN enzyme that generates fatty acids in the liver after an abundant meal.

It wasn’t, however, until five years ago that Dr. Loda and his group began to notice a relationship between elevated levels of FASN to prostate tumors and that the research world began to notice this enzyme’s significance.

“We’ve found that virtually all prostate cancer tumors have a very high level of this enzyme which turns out to transform normal prostate cells into cancerous ones,” said Dr. Loda. “So when we discovered that the FASN enzyme was very active in prostate cancer cells we began to study its effects. We now believe that FASN blocks chemotherapy-induced programmed cell death in prostate tumor cells, a mechanism that is preserved in normal cells.”

To determine FASN’s role in prostate cancer, Dr. Loda purified the gene that encodes the FASN enzyme and injected it into mouse eggs. This created a genetically altered mouse model to study with the consequences of excessive levels of FASN in the prostate gland.

These transgenic mice developed what doctors believe to be a pre-cancerous condition called prostatic intraepithelial neoplasia (PIN) usually within six months to one year after birth.

According to the American Cancer Society a man with a high-grade PIN found on a prostate biopsy has a 20%-30% chance that cancer is present in the prostate. 

After successfully connecting FASN to prostate cancer in the mice models, Dr. Loda’s group studied 750 human prostate cancer patients to find how many tumors expressed the enzyme. The results showed FASN to be present in nearly 65% of the human samples studied and that the expression of this enzyme were inversely related to the rate at which tumor cells died a spontaneous (“suicidal”) death.

The Next Stage
Dr. Loda hopes that with the strong data linking FASN expression to prostate cancer aggressiveness, inhibitors of the FASN enzyme can be synthesized and used to block tumor progression.

“In my research approach I like to use evidence from multiple sources to obtain evidence on the central role of this enzyme in prostate cancer development and progression,” said Dr. Loda.  “In order to commit significant financial resources for drug development, strong research data needs to be obtained from multiple sources.  I think we have done that here.”

According to Dr. Loda there is very good evidence that this enzyme is a prime target in prostate cancer.  Developing inhibitors to target those cancerous cells could lead to an effective treatment for patients.

Pharmaceutical companies have already begun to take interest in FASN as a target. If successfully completed, these drugs would lead to human clinical trials in the future.