Apple chief executive officer Steve Jobs and author Christopher Hitchens, who both recently succumbed to their respective cancers, were among a select few cancer patients to have their entire genomes sequenced. Doctors were hoping to tailor each man’s cancer treatment by identifying genetic mutations within the cancer that might be treatable with certain drugs — an approach known as personalized medicine.
But even after cracking the genetic code, the attempted treatments were not cures. While researchers have made quite a bit of progress with personalized treatments for cancer in recent years, we still have a long way to go, experts say.
For some cancers, such as breast cancer and melanoma, researchers have identified groups of people who respond well to drugs because of the genetic makeup of their cancer cells. In fact, in some cases of leukemia, tailored drugs can keep the cancer in check for many years, said Marc Symons, a cancer researcher at the Feinstein Institute for Medical Research in Manhasset, N.Y.
But for others, the benefit is incremental, extending lifespan by only a few months. And many patients aren’t candidates for tailored drugs at all.
“We’re much better than we were a decade ago,” at treating cancer patients with individualized therapies, said Dr. Daniel Budman, interim chief of hematology/oncology at the Monter Cancer Center, in Lake Success, N.Y. “But unfortunately, a lot of people are still dying of cancer,” Budman said.
Researchers are exploring many avenues to personalized cancer treatment. Ultimately, they hope to better understand cancer itself, what makes it grow, and how people’s individual reactions to cancer make a difference in terms of treatment, Budman said.
“As the knowledge progresses, we get a little smarter about how we treat [patients] rather than indiscriminately [treating] everyone the same,” Budman said.
Whole genome sequencing: Looking for a needle in a haystack
To date, hundreds patients have had their entire genome sequenced for a cancer treatment, Symons said. This approach is rare because sequencing a genome is expensive — around $10,500, according to the National Institutes of Health — and patients must also have their tumor’s genome sequenced (doubling the cost) in order for doctors to compare the mutations in a tumor with those in the rest of a person’s cells.
However, the cost of genome sequencing is rapidly coming down, and Symons said he does not expect this to be a barrier for long.
The biggest challenge is figuring out how to treat the patient once you know the whole genome, Symons said. Researchers must know which mutations are relevant to the cancer’s progression, which are susceptible to treatment, and which drugs should be used to target them, Symons said. “That’s still a black box to a large extent,” he said.
Hopefully, as we sequence more individual genomes, we’ll learn more about what makes certain people susceptible to cancer, and what makes some people better at fighting cancer, Budman said.
Target mutations: Changing our view of late-stage cancers
Breast cancer, lung cancer, leukemia and melanoma are just a few examples of cancers in which specific mutations have been found that can make a tumor susceptible to treatment with certain drugs. In these cases, researchers simply test whether the particular mutation is present — they don’t need to sequence the whole genome, Symons said.
However not all patients with these cancers will have a drug-susceptible mutation. For example, about 50 percent of patients with melanoma have a carcinogenic mutation in a gene called BRAF, and about 10 percent of patients with lung cancer have a mutation in a gene called EGRF. In both cases, drugs have been developed to counter the deleterious effects of the mutation, but for patients without those mutations, the drugs have no effect.
This type of personalized medicine is changing how we think about and diagnose cancer, Symons said. Traditionally, cancer was diagnosed by examining the cancer tissue under a microscope, and assessing whether a tumor has spread to other organs. But researchers are shifting towards a molecular classification of cancers, which categorizes them based on genetic mutations and other molecular characteristics, Symons said.
Drugs that target the right mutations could improve a patient’s outcome, even if the cancer is in advanced stage, Symons said. Eventually, such therapies may change the way people think about late-stage cancer, from a disease that’s often incurable to one that can be managed.
Future cancer treatments
Another approach to personalized medicine is to take a piece of cancer tissueout of the patient, and grow the cancer cells in lab dishes, Symons said. This allows scientists to test out many different drugs on an individual’s cancer to see which ones work best. A similar strategy is to put cells from a patient’s cancer in an animal before testing drugs. So far, this approach has not been used in individual patients, Symons said, but it will be soon.
Some say this strategy has a limited value because human cancers grow in the human body and interacting with the body’s chemistry, Budmansaid.
“You don’t treat the cancer as just an isolated cell. You treat the cancer knowing it’s interacting with that patient,” Budman said.
For instance, researchers may aim to interfere with the blood supply to the tumor, or boost a patients’ immune response to the disease, in order to treat it, Budman said. The best treatments may ultimately be combinations of therapies that together weaken the tumor, and enhance a patient’s ability to fight it, he said.
Pass it on: For some cancers, tailored treatments are available, but researchers must better understand cancer, and how it acts inside an individual, before personalized medicine truly takes off.
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