Cancer Research Q&A

Years ago, it sounded like a cure for cancer was “right around the corner.” What’s the holdup? Why is cancer research so difficult?

Cancer is incredibly complex. It adapts. Even the same type of cancer develops and reacts to treatment differently in different people. Drugs that kill human cancers rapidly and completely in the lab frequently are far less effective when tested in humans. In one instance, the reduced effect was due to the action of a single human enzyme. But which enzyme? And once found, how do we “turn off” the action? Researchers are presented with a never-ending series of questions. But Stehlin scientists are extraordinarily dedicated, and each believes the potential answer is more than worth the complex process.

Cancer isn’t like a virus or bacteriological infection. It’s not a “foreign invader.” A cancer tumor is the result of a normal human biological process (cell division) that’s out of control due to a genetic change or malfunction. The tricky part is determining how to stop the growth of the tumor without affecting normal function, or how to kill the cancer and spare the patient. The first part is easy – Stehlin has been killing cancer cells in its labs for decades – but the last part is astoundingly difficult.

Decades ago, even those involved in its research envisioned a single “magic bullet” cure for cancer. The vast amount of research conducted since (and the explosion of knowledge of human genetics) has completely reversed that picture. Cancer treatment today is becoming very personalized. That’s one reason therapies like the Foundation’s anticancer drug CZ48 are so exciting - CZ48 appears to be effective against several cancer types. A good overview of the progress made in many areas of cancer research may be found in this article –  40 Years On, the Triumphs and Challenges of America’s War on Cancer.

Why does the development of new anticancer drugs/therapies take so long?

There are a lot of steps in the process, each one of which is time-consuming and expensive. And there literally are thousands of regulations and safeguards to be followed. The entire process is governed by the Food and Drug Administration (FDA). Its mandate is huge, and its regulations have been evolving since 1906. FDA describes the process:

Before a drug can be tested in people, the drug company or sponsor performs laboratory and animal tests to discover how the drug works and whether it’s likely to be safe and work well in humans. Next, a series of tests in people is begun to determine whether the drug is safe when used to treat a disease and whether it provides a real health benefit.

Sound simple, right? It isn’t. By design, the process takes years. And recent studies estimate the average cost to get a new drug approved at $55-100 million. Other studies pegged the cost at $1.2 billion. That’s for every new drug, whether it treats cancer or athlete’s foot.

Candidates for a new cancer drug might theoretically include 5,000 to 10,000 chemical compounds. On average about 250 of these will show sufficient promise for further evaluation using laboratory tests on mice. And fewer than ten will qualify for tests on humans. A study conducted by the Tufts Center for the Study of Drug Development covering the 1980s and 1990s found that only one in five drugs beginning Phase I trials are eventually approved for use. CZ48, an anticancer drug developed in the Foundation’s labs, is currently in Phase I clinical trials.

How do clinical trials work?

Clinical trials are the part of testing a new cancer drug or treatment that involves studying its effect in human subjects. The trials follow rigorous protocols (plans), and are divided into phases, each of which is designed to study different aspects/effects of the drug or therapy.

Phase I tests an experimental drug or treatment on a small group of people (20-80) to evaluate its safety, determine a safe dosage range, and identify side effects. If successful, the study moves to Phase II.

Phase II involves a larger group (100-300). Its goal is to test the drug’s effectiveness and to continue to gauge its safety.

Phase III groups are large (1,000-3,000) and are used to confirm the drug’s effectiveness, to monitor its side effects, and to compare it to other treatments.

Finally, Phase IV performs post-introduction studies to collect information about the drug’s risks, benefits, optimal use, etc.

For more information, especially if you are considering participating in a trial, see Clinical Trials.gov.

Why doesn’t Stehlin concentrate on a particular type of cancer?

Sometimes we do. For example, after Foundation researchers discovered the selective sensitivity of cancer cells to heat, Stehlin physicians were the first to treat advanced melanomas of the arms and legs using a combination of heat and chemotherapy (hyperthemic perfusion).  This procedure essentially eliminated the need for amputation and improved survival rates by 300 percent.

But we don’t limit our focus in every case. In the development of CZ48, laboratory testing revealed the compound exhibited a broad spectrum of anticancer activity against breast, lung, colon, pancreas, and bladder carcinomas, and against melanomas and DRCT sarcomas. Going forward, we may concentrate CZ48 testing on a particular type for clinical trials, but will continue to look for answers across the cancer horizon.

What are “nude” mice, and why are they important to research?

Nude mice were derived from a strain of mice with a genetic mutation. That mutation resulted in an inhibited immune system due to a greatly reduced number of T cells. The phenotype (main outward appearance) of the mouse is a lack of body hair, which gives it the “nude” nickname. The nude mouse is valuable to cancer research because it can receive human tumor grafts and allow the cells to grow as a human (not mouse) tumor without mounting a rejection response.

Stehlin Laboratory Director Dr. Beppino Giovanella pioneered the development and use of the nude mouse in cancer research, establishing that if an anticancer drug works against a human tumor implanted in the nude mouse, it most often will also be effective in treating the patient from whom the tumor was removed.  Today the nude mouse represents the final non-human studies required by the National Cancer Institute for determining the effectiveness of anticancer drugs.

Where can I learn more?

Obviously, the Internet has more information about cancer than anyone could possibly read, so “where to start” is an issue. See our Links page for some suggestions. Another entertaining source is The Emperor of All Maladies: A Biography of Cancer by Dr. Siddhartha Mukherjee. This 2010 book was described by Publishers Weekly as a “sweeping epic of obsession, brilliant researchers, dramatic new treatments, euphoric success and tragic failure, and the relentless battle by scientists and patients alike against an equally relentless, wily, and elusive enemy.” Sounds like a typical day at CHRISTUS Stehlin Foundation.