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Leveraging the Power of Genomics

A Report from the National Cancer Institute


Photo by Cancer Type

Ten years ago, a collaboration of hundreds of scientists announced it had finally completed sequencing the human genome – the location map for all the bits of genetic information that tell our cells when and where to develop, how to grow and feed them­selves, and eventually, how to die. For diseases like cancer, this new under­standing confirmed what researchers and physicians had begun to suspect and had found the first evidence for several decades earlier: Cancer is not a single disease, but a constellation of genomically distinct and identifiable diseases. In fact, even within a single person, some tumors may not be the same cancer but could be as different, genetically, as night and day.

This detailed genetic understanding of cancers is the basis for what many are now calling precision medicine. By knowing the specific genomic dis­position of an individual’s cancer or cancers, doctors can begin to prescribe increasingly tailored treatments or drug combinations targeting the specific genetic mutations that led to the cancer in the first place. Precision medicine will affect more than diagnosis and treatment – genomic information could tell doctors which people are at higher risk of developing some cancers, who might benefit from preventive care or more frequent screening, and even which people are more likely to survive their cancers and what their quality of life will be.

In 2003, the ink was hardly dry on the printing presses that published the sequence of the human genome before critics began to question why we didn’t already have immediate clinical out­comes driven by completion of the human genome sequence. In many cases, what the human genome had given us was a very long and very detailed cast of characters – but not the script, the plot summary, or the roles the characters would play.

By knowing the specific genomic disposition of an individual’s cancer, doctors can begin to prescribe increasingly tailored treatments.

Today, however, cancer research is leading the field in applying genomic information to prevention, screening, diagnosis, and treatment. The leading edge of the National Cancer Institute’s genomic research – conducted jointly with the National Human Genome Research Institute – is a program called The Cancer Genome Atlas, or TCGA (the acronym comes from the names of the base pairs that make up DNA). TCGA began as a three-year pilot project in 2006 for a very small set of cancers to see whether it would be possible to identify, catalog, share, and compare genetic changes among differ­ent tumor types. The successful pilot program has been expanded to now include more than 20 types of cancer, those having the most significant im­pact on individual and public health.

To date, TCGA researchers have published atlases for several of these cancers, among them glioblastoma; lung, ovarian, colorectal, breast, and endometrial cancers; and acute myeloid leukemia. Findings have included the following:

Adult glioblastoma multiforme (GBM) appears to be four distinct molecular subtypes, each of which responds differently to aggressive chemotherapy and radiation, which could set the stage for individualized treatment strategies.
In contrast to many other adult cancers, acute myeloid leukemia (AML) actually has very few genetic mutations – 13 in AML compared with hundreds in solid tumors, like breast, lung, or pancreatic cancer. Rather, AML seems to be driven by epigenetic factors – chemical changes that do not affect the underlying DNA sequence.
Endometrial cancers currently fall into two categories based on how they look under a microscope, and the two types are treated differently and usually have different outcomes. But geneti­cally, it appears that at least some type I tumors are more closely related to type II and may benefit from a similar course of treatment; conversely, some morphologically similar tumors may be very different genetically and require different treatments.
For lung squamous cell carcinoma, researchers identified several promising new drug targets that involve genetic switches that turn on or off critical cellular functions.
Colon and rectal cancers are geneti­cally indistinguishable regardless of whether they arise in the colon or the rectum, and they can be treated as a single type of cancer.
Researchers studying ovarian cancer identified patterns for 108 genes associated with poor survival and 85 associated with better survival. More­over, in comparing the genomic analysis of breast and ovarian cancers, at least one type of genetic pathway seems to be mutated in both, leading doctors to believe that some drugs currently used for breast cancer could also be effective against some ovarian cancers.

Cancer research is leading the field in applying genomic information to prevention, screening, diagnosis, and treatment.

These findings and others from TCGA, many of which are now inform­ing clinical trials and novel treatment approaches, are just the vanguard of genomic information that will rewrite cancer treatment and survivorship in the years to come. In 2013, more than 14 million Americans are living with cancer, a number that, based on current prevalence trends, is likely to grow to more than 18 million by 2022. Sixty-four percent of these survivors have been living with cancer for five years or more; over the next decade, the size of the cohort surviving five years or more will increase by another third. Precision medicine based on genomics has the potential to completely rewrite these numbers so that surviving – and even thriving – long term with cancer is the expectation for most Americans after a diagnosis of cancer.

The research needed to make this future a reality, however, is imperiled by cuts to biomedical research that threaten to slow or stall the progress we have made in recent years in controlling can­cer. At the National Institutes of Health, the budget plan known as sequestration will cut between one and two billion dollars from the fiscal year 2013 budget. All areas of science, including cancer research, will be affected – the seques­tration set an arbitrary 5 percent cut across the board. The impact of these cuts means that NIH overall will fund 700 fewer competitive research project grants than it did in fiscal year 2012, and the pipeline of new cancer drugs target­ing specific genetic mutations or cellular pathways with fewer side effects almost certainly will shrink. Research to under­stand the issues facing people living with cancer and improve the quality of life for cancer survivors will also be affected.

The nation – including cancer survivors, their friends, and their fami­lies – would be better served by a robust cancer research funding plan that is driven by scientific advances rather than by arbitrary budget cuts. NCI is work­ing actively with foundations, charities, and others to explore ways to help make up the shortfall created by sequestration through challenge grants, crowd fund­ing, and other innovative means to fund biomedical research. However, there is no substitute for stable, secure funding for cancer research. Our advocates and supporters can lend their voices to the growing chorus of concern over budget cuts in biomedical research, and help secure the future of funding for con­trolling cancer and ensuring long and productive lives for cancer survivors.

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Since 1994, the National Cancer Institute has written an exclusive annual report for Coping®’s July/August Celebration issue.

This article was published in Coping® with Cancer magazine, July/August 2013.