In the future fight against cancer, doctors are looking beyond afflicted organs—whether lung, brain or stomach—and finding new answers by disrupting the genetic mechanisms of specific tumor cells.

Novel cancer drugs at the center of a major medical meeting this week point to a future in which patients are more routinely tested for gene mutations underlying their cancer to match them with a targeted treatment.

That would represent a major shift from the current medical paradigm, in which a patient's disease is more closely identified with an area of the body to determine what battery of chemotherapy or other one-size-fits-all regimen is needed.

"We are not waging a single war against a single enemy," said Dr. Harold Varmus, director of the National Cancer Institute. "It is literally hundreds of different diseases ... in every domain of cancer there is a puzzle to be figured out."

Advances in genetic sequencing are helping scientists to solve some of those puzzles, and the number of experimental compounds has mushroomed. New data on several targeted drugs released this week at the annual meeting of the American Society of Clinical Oncology showed the progress made in making this mode of treatment a reality after many years of research.

"We have proof of principle in some tumors where we have identified a target ... we can actually make an enormous difference in the outcome," said ASCO President Dr. Michael Link.

In one of the most talked-about studies, advanced melanoma patients given an experimental pill, vemurafenib, developed by Roche and Daiichi Sankyo were 63 percent less likely to die than patients given chemotherapy.

Vemurafenib is designed for use in patients with tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow. About half of all melanomas have the genetic aberration.

"This agent is producing responses that have really been unheard of with chemotherapy," said Sandra Horning, head of global development for oncology at the Roche's Genentech unit.

She declined to talk about market expectations for the drug, but did say Roche would launch it with a companion test for diagnosing the BRAF mutation.

Another study presented at ASCO found that matching therapies, most still experimental, to the genetic markers led to higher rates of tumor shrinkage and survival for patients with advanced cancer.

And while there is still a high correlation between genetic mutations and specific types of cancer as we know them, researchers are also finding links between the different categories, opening up new possibilities for treatment.

"What we are finding out is that the molecular abnormalities cross tumor types," said Dr. Razelle Kurzrock, professor and chair of MD Anderson's Department of Investigational Cancer Therapeutics, which conducted the study.


Unlike traditional chemotherapy drugs, which work by interfering with the entire body's system of cell replication, newer targeted drugs aim to block specific pathways that cancer cells use to grow and reproduce. The targeted therapies ideally cause fewer harsh side effects, but they also work only in patients with the specific gene mutation.

Cancer drug sales—which doubled between 2005 and 2010—are expected to continue leading pharmaceutical industry growth. The sector will grow 8 percent a year, reaching $93 billion in 2016, according to Natixis. Much of that growth is expected to come from such targeted therapies, which have already revolutionized the treatment of a few specific cancers, such as leukemia, certain stomach tumors and a subset of breast cancers.

Close to 900 more cancer medicines are currently being tested in humans, according to the NCI.
But the new drugs are also expensive, with a course of treatment typically priced at tens of thousands of dollars.

"The cost issue is tremendously important," said Dr. Robert Burger, director of Fox Chase's Women's Cancer Center in Philadelphia. "The political lobby, the pharma industry, and healthcare insurance providers need to sit down and figure out how to make these types of treatments more affordable."

Also fueling the cost issue, major drugmakers are looking at ways to combine targeted therapies. They say it will lead to an even more effective treatment by blocking multiple pathways needed by cancer cells.

The combination of two experimental pills developed by GlaxoSmithKline PLC—one BRAF-blocker and another designed to inhibit a gene known as MEK—were shown in an early-stage trial to shrink tumors in a majority of patients with advanced melanoma. Roche has teamed with Bristol-Myers Squibb to test vemurafenib in combination with Bristol's ipilimumab, an antibody designed to spur the body's immune system to fight off the cancer.

Since most tumors eventually find a way to get around blocked pathways, "there is widespread understanding that we are going to need to learn how to combine two or more targeted therapies to block the main road and the side road and the dirt road," said ASCO Chief Executive Dr. Allen Lichter.