A researcher at Stony Brook University's School of Medicine has developed a novel strategy she hopes will prevent cancer-drug resistance, a major problem that largely afflicts patients whose disease has recurred and spread.
Countless patients worldwide, doctors say, lose the battle against all forms of cancer because their tumors repel the treatments. Dr. Sabine Brouxhon's candidate therapy is designed to boost the odds to favor patients.
The university sees her approach as so promising, it has entered into a licensing agreement with the California biotech startup CadheRx Therapeutics in La Jolla. The plan is to develop and market a treatment based on Brouxhon's work.
"Our lab has discovered a novel antibody-based cancer therapy that acts through a completely different mechanism of action compared to existing drugs in the industry," she said.
Despite the keen specificity of drugs known as targeted therapies -- hailed in recent years as conceptual breakthroughs in treatment -- cancers still develop resistance to them. Patients who have run the gamut of therapies can be left without options.
Cancer cells across a range of malignancies possess a deep archive of biological maneuvers enabling drug resistance, doctors say.
Drs. Pasi Janne and Levi Garraway of the Dana-Farber Cancer Institute in Boston asserted three years ago in the journal Cancer Discovery: "All successful cancer therapies are limited by the development of drug resistance."
Brouxhon's newly developed strategy addresses cancers that have acquired resistance to the therapies known as monoclonal antibodies, such as Herceptin, a targeted drug developed for an aggressive form of breast cancer, and Erbitux, a targeted colorectal cancer medication.
Each of these therapies functions by blocking specific tumor-driving proteins. Although effective for a while, cancer cells can eventually use any one of numerous mechanisms to outwit the drugs.
Brouxhon's evolving approach is designed to block multiple tumor proliferation and resistance pathways. "It's extraordinarily exciting to see a basic research discovery from a Stony Brook University scientist turn into something that might improve people's lives in a very powerful way," Dr. Samuel L. Stanley Jr., Stony Brook's president, said in a statement. "Cancer affects millions of people worldwide, and Dr. Brouxhon's work on this new anticancer technology offers continued hope in the fight against many forms of cancer," Stanley said.
Sean Boykevisch, Peter Donnelly, Ben Hsiao and Nancy Daneau, from the university's Research Office, played critical roles in helping to license the technology.
The Stony Brook research, however, isn't the only antiresistance work underway. Scientists at numerous institutions regionwide -- Cold Spring Harbor Laboratory, Memorial Sloan-Kettering Cancer Center, Columbia University, New York University, the Tisch Cancer Institute at Mount Sinai Hospital and Weill Cornell School of Medicine -- are tackling the issue.
Tumor biologists call the resistance phenomenon one of the most vexing facing cancer patients today and note conventional chemotherapeutic medications were the first to which cancer cells demonstrated resistance decades ago.
Brouxhon's research zeros in on the class of molecules known as E-cadherins, a vital group of "adhesion" proteins that underlie a vast range of normal cell functions. These cell-surface molecules are noteworthy as the "biological glue" allowing individual cells to stick to each other and form tissues.
Brouxhon has found, however, that once healthy cells have transformed into malignant ones, derivatives of the cadherins play roles in tumor-cell proliferation and cancer-drug resistance.
"E-cadherins help cells attach to each other," Brouxhon said, but with cancer cells, the cadherins "flow into the tumor microenvironment and the shed protein is called soluble E-cadherin."
Once shed, E-cadherin levels rise dramatically, contributing to enhanced cancer cell proliferation, migration and drug resistance. Brouxhon said her antibody blocks the multiple avenues the molecules use to drive cancer growth.
Biologist Benjamin Weeks, a professor at Adelphi University who has studied another type of cellular adhesion molecule, commended Brouxhon for her approach. "There are a number of researchers who have been looking into adhesion molecules and their role in cancer and inflammation. This is a very important area," said Weeks, who has explored the possible role adhesion proteins called integrins play in cancer.
Brouxhon, meanwhile, said her work on the antibody began in 2010. She is uncertain how long it will take for the startup company to bring a drug to fruition.
However, laboratory tests at Stony Brook have demonstrated that her antibody is powerfully inhibitory with a high degree of specificity. These factors, she said, decrease the likelihood that cancer cells will recruit the array of interconnected genes that play a role in repelling medications.