Researchers at Lehman College have discovered a novel mechanism for killing cancer cells and are engaged in clinical trials for a variety of human tumors. It is a new generation of medication that could give doctors fresh alternatives in combining drug therapies with radiation or chemotherapy, while lessening side effects on the patient.
The team has identified the molecule that plays a pivotal role in killing human cancer cells while not affecting normal cells. The discovery centers on the interaction of two proteins that promotes the death of cancerous cells, and makes tumors more sensitive to radiation and chemotherapy.
Lead researcher Professor Moira Sauane and her team published their discovery in August 2013 in the journal Biochemical and Biophysical Research Communications. Now with a patent pending, they are applying the knowledge to begin designing more effective drugs to attack cancer and make it more treatable.
For fifteen years, gene therapy researchers have known that a certain protein – Interleukin-24 (IL-24) – kills cancer cells while acting benignly toward normal cells. But they have never been sure why.
Prof. Moira Sauane and her researchers determined that Interleukin-24 is effective against cancerous cells because of its interaction with a protein known as Sigma 1 Receptor. They discovered that when Interleukin 24 is introduced into an abnormal cell, it binds to Sigma 1 Receptor, which begins the process of killing the cell.
“It is like the falling of the first domino,” said Prof. Sauane. “We had found most of the pathways that IL-24 trigger to induce tumor-specific cell death. But we were missing the first piece, the beginning of the cascade that leads to the death of a cancerous cell.”
Now that they know where that chain reaction begins, researchers can build drugs to kill cancer cells more efficiently. The team is working with Professor Gustavo López in the Lehman College chemistry department on computer modeling to discoverwhich regions of the two proteins bind together. The next steps are to create smaller molecules that bind more easily and formulate a drug that is more likely to attack cancer cells. Such a drug would be more stable in the human body and a much more efficient treatment. It could be used in combination with radiation or chemotherapy to kill cancer cells with fewer adverse effects to the patient.
“Cancer represents a significant worldwide public health problem,” says Prof. Sauane. “To advance new anti-cancer therapies, which are already being used in patients in clinical research, it is imperative to understand the molecular mechanisms involved in the action of anti-cancer agents.”
Prof. Sauane’s research focuses on studying therapeutic viruses that kill only tumor cells. The project aims to define the underlying mechanisms of these anti-cancer genes, which will result in improved outcomes of therapeutic strategies for cancer and lead to the discovery new therapeutic strategies to complement existing strategies. Multiple studies have demonstrated that Interleukin-24 kills a broad spectrum of human cancer cells without adversely affecting normal cells, including: melanoma, malignant glioma, fibrosarcoma and carcinomas of the breast, cervix, colon, rectum, liver, lung, ovary and prostate.
The team included Prof. Moira Sauane, Professor Stephen M. Redenti, and several undergraduate and graduate students: Winchie Do, Cynthia Herrera, Jason Mighty, and Maria Shumskaya.
“I am very proud of my participation in this research, even though I am still an undergraduate student,” said Winchie “Chi” Do, a senior biochemistry major. “It has been an exciting experience to collaborate with the group and study under someone as passionate as Professor Sauane.”
Prof. Sauane, a native of Buenos Aires, has taught at Lehman since 2012. She has been studying new cancer treatments for nearly two decades, focusing on gene therapy – inserting genes into individual cells to manipulate or destroy cancer cells.
View or download photos of Prof. Sauane and her students at work.