MAKING IT PERSONAL

The treatment options for many kinds of cancer have improved tremendously over the years. But two particular challenges have dogged cancer researchers for as long as we have been treating patients with this disease.

Why do some patients benefit from a course of therapy while others, apparently with the same or similar cancer, don’t?

How do we tailor all of our therapies – surgery, radiation, chemotherapy – to optimize their effects against cancer cells while steering clear of healthy cells and tissue?

We are becoming increasingly skilled at addressing both of these questions, and are truly excited by the opportunity to greatly improve our treatment approaches. By further connecting specific therapies to better defined groups of patients, we are sharpening our attack on cancer and developing ways of making treatments specific to an individual patient.

Tailoring therapy is important. Because the consequences can be so dire, particularly when the disease has reached advanced stages, it’s easy to think of “cancer” as a monolithic disease. Cancer actually comprises more than 200-300 separate diseases, with different types affecting the same organ. For reasons we don’t yet fully understand, patients with one type of cancer can actually vary substantially from one another. As a result, general approaches to treatment fail many patients.

The focus must now turn to targeted approaches, using new drugs that stifle a specific molecular aspect of one type of cancer. Two spectacular examples of this are Gleevec for treating chronic myeloid leukemia (CML) and Herceptin for treating types of breast cancers that overproduce a certain growth-related protein.

Before Gleevec, half of CML patients died within five years. Today, more than 90 percent reach that milestone. Herceptin, taken with chemotherapy, cuts the recurrence of a particularly aggressive form of breast cancer by 50 percent and reduces a patient’s risk of dying of the disease by 33 percent.

However, even these two drugs don’t help every patient with the relevant molecular target. And medications initially aimed at one type of cancer have sometimes serendipitously succeeded against other types. Gleevec is also quite effective against gastrointestinal stromal tumors.

Many other cancers don’t have an obvious single target, but instead rely on multiple molecular pathways and genetic changes that create an environment where they can thrive. Ferreting out the appropriate targets takes time, but progress is being made. This is why it is so important to support research. Current research projects are aimed at finding new targets and better drugs to attack those targets.

Take colorectal cancer, my own research and clinical specialty, for example. There are at least five or six different types of this disease, and within those types individual patients can differ substantially.

The targeted therapy Erbitux blocks a growth-promoting protein common in most types of colorectal cancer. The results in some colon cancer patients have been remarkable. Unfortunately, like many new targeted drugs, Erbitux seems to help only about 10 percent of patients. Researchers have found that certain colorectal cancers with a specific genetic mutation are unaffected by Erbitux. Screening of patients for this mutation has begun – a vital step in more effectively targeting the drug to those who will benefit the most. It’s important to know whether a patient is a candidate for this therapy in order to save precious time and avoid a course of treatment that may be doomed to fail.

Erbitux also has been approved for head and neck cancer, where further targeting refinement is under way. Instead of having one drug that treats all patients with a specific type of cancer, the future belongs to drugs that treat patients with common molecular targets across several types of cancer. Instead of being classified according to the affected organ, cancers may eventually be typed by their molecular characteristics.

In the meantime, it’s vital to better characterize the drugs that we have now and to match them to appropriate targets present in the tumor.

For example, four oral medications are being tested in an unusual lung cancer clinical trial at my home institution, The University of Texas M. D. Anderson Cancer Center in Houston. Lung cancer patients have a biopsy conducted on a tumor sample before being randomized to receive one of the drugs. Eight weeks later, they are evaluated again, including another biopsy.