U.Va. Researcher Aims to Make Cancer Manageable

Aug. 12, 2009 — Until recently, treatment for cancer – though quite sophisticated in practice – has been limited to three basic approaches: killing cancer cells by removing them surgically, blasting them with radiation or poisoning them with chemotherapy. The goal is to destroy all malignant cells, curing the cancer and preventing remission. Even when these three approaches are used in combination and treatment is administered repeatedly, some cancer cells survive, and the disease can and does recur.

In a way, the flaw in this line of attack has been its ambition. In the last few years, a number of treatments have been approved with the more modest goal of simply holding cancer in check. They do this by blocking the cellular pathways that enable cancer cells to grow and flourish.

Tau Therapeutics, based on intellectual property patented at the University of Virginia by Timothy Macdonald, a medicinal chemist, and former faculty member Lloyd Gray, a pathologist, specializes in developing cancer-fighting drugs that control the calcium T-channel in cells – tiny transient openings in the cell membrane that allow calcium, which is necessary for cell proliferation, to enter the cell.

"If we can stop the tumor cells from dividing, we can provide a meaningful increase in lifespan," Macdonald said.

"Tau's method represents an advance over other treatments to halt the growth of cancer," says Tau's president and CEO Andrew Krouse. "That's because all pathways for tumor cell proliferation – for tumor growth as well as for the new blood vessels needed for tumor growth – converge at the point of the calcium T-channel, CaV3.2, that Tau has patented."

Tau's vision is to block CaV3.2, thus allowing cancer to be managed as a chronic disease like diabetes or heart disease.

Tau's initial focus is to reposition existing calcium-channel blockers that have already been approved for other conditions, a tactic that can decrease the time to bring the new cancer medications to market.

For instance, it will be sponsoring a clinical trial to test the efficacy of mibefradil, a calcium-channel blocker that had been approved for the treatment of hypertension and chronic angina. Tau envisions mibefradil being used in combination with other medications to treat a wide range of cancers.

Tau's longer-term strategy involves building libraries of small molecules that could control calcium-channel processes. It has patented two libraries, synthesized and tested more than 400 compounds, and has identified several viable substances for development.

The first of these, TTL 1177 – a drug targeted at colon cancer – is undergoing laboratory testing, and Tau could file an investigational new drug application with the U.S. Food and Drug Administration within the next 18 months.

Tau's approach could have several advantages. Unlike conventional cancer treatments, Tau's medications will not destroy healthy tissue; because calcium T-channels only appear during adulthood as part of a pathological condition like cancer, T-channel blockers focus only on cancer cells. In addition, molecules in Tau's pipeline can be administered orally, an improvement over drugs like Avastin that must be injected.

Ultimately, Tau's goal is to be the world leader in producing calcium T-channel drugs for the personalized treatment of cancer.

"We envision combining early detection through diagnostic screening of the calcium T-channel, biopsies for the particular expression of the target, and the prescription of complementary drugs based on the molecules in our library," Krouse said. "In this way, we hope to treat cancer like any other chronic disease, extending both the length and quality of life of people with cancer."

— By Charlie Feigenoff