UCR Professor Dr. Maurizio Pellecchia and his research team have discovered a way of tracking cancer cells with the chemotherapy drug Paclitaxel. The drug tracks cells that cause tumor metastases when secondary malignant growths form at a location separate from a primary site of cancer.
Paclitaxel is typically used to locate rapidly dividing cancer cells in order to target tumor growth. It is a well-known cytotoxic (toxic to living cells) drug that effectively stops cellular division. Because it is not selective to cancer cells, it causes severe side effects, killing normal cells that divide at a fast pace, such as hair follicles or mucosal membranes. Cytotoxic drugs target cells in two different ways; by attacking cancer cells or by suppressing tumor cell growth signals. Dr. Pellecchia explained the significance of his discovery in an interview with The Highlander. “Our work focuses on an oncogene (named EphA2) that confers cancer cells the ability to migrate form the primary tumor, enter blood circulation and eventually adhere to other tissues and forms metastases,” wrote Pellecchia.
His research focuses on targeting the receptor on the surface of the cancer cells and he explained that there are two primary traits they look out for. The first of these two is that it allows cancer cells to enter blood circulation, which contributes to metastases. The second characteristic is when the EphA2 targeting agent binds to the receptor, the receptor recoils inside the cancer cell where the proteolytic enzymes destroy it. The agents that target the EphA2 receptor cause its disruption within the cancer cell, and Dr. Pellecchia’s team took this property of agents a step further. He explained that they did so by “chemically linking a potent cytotoxic agent to 123B9, cancer cells that are rich in EphA2 would transport the toxic agent inside the cell, like a Trojan horse, hence effectively killing it.”
Dr. Pellecchia claims that the ultimate aim behind this research is to lead to better cancer treatments. The main contribution this research would make is allowing for the agent to capture and kill circulating tumor cells before they cause metastases. He also hopes the agents they work with will spare normal cells, as these do not present the EphA2 receptor. This could prevent cancer treatment from leading to hair loss. Pellecchia wrote, “We anticipate a significant reduction of the common side effects of chemotherapy.”
However, Dr. Pellecchia still sees a long road to therapeutic trials for humans. A lot of the cause is simply that it takes a significant amount of time before an experimental drug reaches the clinics due to manufacturing and safety testing. He also pointed to the lack of resources allocated to academic institutions. “Many promising therapeutics often never reach the patients, due to lack of funding to support these activities,” said Dr. Pellecchia. On average, a minimum of $2 to 3 million is needed to file an investigational new drug application with the Food and Drug Administration and start a clinical trial in oncology.
Dr. Pellecchia received his bachelors of science in organic chemistry at the University of Naples Federico II in Naples, Italy before receiving his Ph.D. in pharmaceutical chemistry at the same institution. His laboratory focuses on pharmacological tools in the areas of cancer, neurodegeneration and potentially other disease areas. Per his website, a central theme of his research is the advancement of promising agents into potential therapeutics.
