The doctor looks at her patient’s test result and sighs – telling a patient he has metastatic melanoma is hard. Chemotherapy probably won’t prolong survival. Immunotherapies help in some cases, but make patients sick. Surgery and radiation are mostly used to relieve symptoms. Most patients with this widespread malignant skin cancer will live only six to ten months.
Or at least that was the scenario five years ago. Things have changed. Researchers have discovered that melanoma can be divided into several categories depending on the tumour’s genetic makeup. One type with a mutation in a gene called BRAF can be treated with a drug called vemurafenib, which can bring the development of some tumours to a dramatic halt and double some patients’ life expectancy.
Innovations in the genetic sequencing of tumours are bringing about a revolution in personalised cancer therapy. To adapt, doctors and researchers are stepping outside their traditional roles. Today’s oncologists are informing the research of scientists, while geneticists and bioinformaticians are beginning to shape the treatment of individuals in real-time.
“I’m at the interface of three or four interesting worlds that have previously talked, but not interacted with as much overlap as they do now,” says Nikhil Wagle, an oncologist at the Dana-Farber Cancer Institute and the Broad Institute in Boston, Massachusetts. “It’s extraordinary.”
Wagle may be a cancer doctor, but his role is not limited to patient care. A typical week involves sifting through sequencing data with computational biologists and discussing functional gene studies with lab-based researchers. The result is a better understanding of how cancers differ, he says. “The size of the groups that we are putting people into is getting smaller and smaller.”
The role of the cancer researcher is also evolving. Geneticists and bioinformaticians may increasingly be called upon to help make decisions about the best course of treatment for an individual. A handful of institutions have already started to make genetically-informed treatment choices for patients (see “Doctor, doctor”, below).
That scenario is still uncommon, though. Even at research centres with access to sequencing equipment and supercomputers to process the information, the medical system is lagging behind advances in genetics. For one thing, there are many unanswered questions. Will insurance companies foot genetic sequencing bills for all individuals with cancer, or only those with advanced disease and few treatment options? What if a person’s best treatment option involves an expensive drug that is not yet approved by the US Food and Drug Administration for that particular tumour? And then there’s the problem of how to turn genetic sequencing data into a treatment decision. Sequence a tumour and you’re likely to find thousands of mutations, many essentially unknown to science. As Wagle and his colleagues put it, the genomics superhighway has met the bike path of medical practice.
In the meantime, a number of new courses are being offered to prepare researchers for this more clinical role, and to tailor their research accordingly. The idea is that doctors can help scientists better understand the cancers they’re working with, and choose the best research questions.
Curtis Pickering, a molecular geneticist by training, was granted a TRIUMPH (translational research in multi-disciplinary programme) fellowship at MD Anderson Cancer Center in Houston, Texas. The programme, which exposes postdoctoral fellows to clinical medicine, offered Pickering the chance to shadow clinical doctors, and take a first-hand look at cancer care.
“Working with physicians to understand how patients are treated, and what a tissue sample goes through before it gets into our hands, actually is necessary for us to properly design our research,” says Pickering.
Robert Sikes, director of the Center for Translational Cancer Research at theUniversity of Delaware in Newark, thinks these programmes are vital for cancer researchers. “It keeps people focused on the disease rather than the molecule,” he says.
Joining the revolution
To be a part of the translational cancer revolution, it’s important to get where the action is. “You have to be around not just cancer researchers but oncologists and pathologists,” says Marc Ladanyi, a molecular pathologist at the Memorial Sloan-Kettering Cancer Center in New York. “For this kind of work, it’s becoming very disadvantageous to be in a university department that’s not connected to a cancer hospital.”
It’s also vital to get a handle on disciplines outside your own area of expertise. “This is team science at its finest,” says Elaine Mardis, co-director of the Genome Institute at Washington University in St Louis, Missouri. Beyond cancer genetics, a basic understanding of clinical care, pathology, and pharmacology will be useful. “When you get involved with a group, you learn by osmosis exactly how all this stuff works,” she says. “It really takes all of those areas of expertise to work together.”
Translational cancer research also involves a host of other players. When a genetic mutation pops up, pharmacologists can alert both researchers and clinicians of new or in-development drugs targeting that mutation that they might try. Materials scientists play an important role in developing tumour-cell scaffolds that enable human tumours to be studied in animal models, which can offer a platform for testing whether or not a drug will work. Genetics counsellors help patients navigate an increasingly complex set of treatment choices.
Some skills are especially valuable. According to Ladanyi, there are never enough bioinformaticians and computational biologists. Carl Morrison, executive director of the new Center for Personalised Medicine at Roswell Park Cancer Institute in Buffalo, New York, agrees that opportunities for the computer-savvy are plentiful. “If you have IT or bioinformatics skills, your chances of being employed in cancer science or cancer clinical care increase by a hundredfold,” he says.
Genomics-based cancer care is too big for any one discipline. “We’re still going to need the very pure basic scientists and we’re still going to need the person who sees patients all the time,” says Roy Herbst, oncologist at the Yale Cancer Center in New Haven, Connecticut. “But in order to bridge that gap, we’re going to need a greater number of people who can live in both worlds.”
Cancer therapy isn’t what it used to be. Clinical doctors are no longer the only ones who decide on the course of a patient’s treatment – cancer scientists are beginning to use genetic sequencing data to help them make the decision.
A handful of cancer hospitals have already assembled teams of clinical doctors and scientists that use genomic sequencing to offer real-time hope to cancer patients.
The Dana-Farber Cancer Institute and the Broad Institute, both in Boston, Massachusetts, recently launched the CanSeq programme to do just that. Biopsies taken from people with cancer are genetically sequenced before the data are crunched by computer programmes. Both physicians and scientists then annotate the results with findings from recently published studies. The entire package is then reviewed by a genomics tumour board made up of clinicians, lab-based scientists and genetic counsellors. As a team, the group use the information to advise the individual’s oncologist on the best course of action.
A similar programme is underway at the Mayo Clinic in Rochester, Minnesota. Here, once a person with cancer has their tumour sequenced, a team that includes bioinformaticians, lab directors and physicians pores over the results. Each genetic mutation is assigned a grade – familiar, actionable mutations are scored an “A”, while more mysterious ones are assigned a “D” grade. In those cases, MDs and PhDs join forces to look for an existing treatment or clinical trials in which the person might be enrolled.
It’s an extension of how lab directors have long interacted with doctors, says Matthew Ferber, at the Mayo Clinic’s Center for Individualised Medicine. “In the past, it really was much more a case of catapulting results over the wall,” he says. “Nowadays, operating in our individual silos is no longer sufficient.”
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