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Squelching ovarian cancer: the not-so-silent killer

The search continues for new biomarkers, better outcomes and, yes, cures for this deadly disease

Sept. 17, 2018 | By Diane Mapes / Fred Hutch News Service

drawing of ovarian cancer patient

Illustration by Kimberly Carney / Fred Hutch News Service

Despite its long-standing nickname, ovarian cancer isn’t really a silent killer. There are symptoms; it’s just that they whisper or are commonly mistaken for something else, like aging or irritable bowel syndrome. As a result of this — and the lack of therapies for advanced disease — ovarian cancer continues to kill nearly 15,000 women a year in the U.S., most of whom are diagnosed at a late stage.

There's been recent progress in treatment: Three new targeted drugs called PARP inhibitors have helped many ovarian patients, especially those with inherited BRCA1 or BRCA2 mutations, which account for about 15 percent of all ovarian cancers. Combinations of old and new drugs have also shown promising results.

But there is much left to do to catch and squelch this killer.

Researchers at Fred Hutchinson Cancer Research Center are on the case, primarily in three of ovarian cancer’s most problematic realms: early detection and screening; differentiating the patients who won’t respond to standard chemotherapies from those who will; and developing new treatments, like immunotherapies, to beat back advanced disease.

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Washington’s Andy Hill Cancer Research Endowment awards $1.5M to 3 Fred Hutch researchers

Scientists will use funds to expand research in graft-vs.-host disease, chemoprevention and cancer immunology

Sept. 14, 2018 | By Jill Christensen / Fred Hutch News Service

Drs. Evan Newell, Geoffrey Hill and Thomas Kensler

Andy Hill Cancer Research Endowment recipients Drs. Evan Newell, Geoffrey Hill and Thomas Kensler, all of whom were recruited recently to Fred Hutch.

Photos by Robert Hood / Fred Hutch News Service

Three researchers at Fred Hutchinson Cancer Research Center recently were awarded a total of $1.5 million from the Andy Hill Cancer Research Endowment, a public-private partnership that supports cancer research in Washington. Until recently, the fund was known as the Andy Hill Cancer Research Endowment (CARE) Fund.

The awardees, all recent recruits to Fred Hutch, each of whom received individual grants of $500,000, are:

  • Dr. Geoffrey Hill, a renowned bone marrow transplantation physician-scientist whose research focuses on better understanding of a transplantation side effect called graft-vs.-host disease, or GVHD.
  • Dr. Thomas Kensler, an expert in carcinogenesis and chemoprevention whose laboratory focuses on using chemoprevention to establish safe, economical, and effective means for reducing cancer risks related to unavoidable environmental exposures.
  • Dr. Evan Newell, a leading immunologist whose research focuses on using new technologies for identifying specific, accurate biomarkers of human health and disease, including cancer.

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How chromosomes find a happy medium

Hutch scientists show how chromosomes communicate to balance crossovers during sex-cell formation

Sept. 14, 2018 | By Sabrina Richards / Fred Hutch News Service


An illustration of trisomy, the state of having three copies of the same chromosome (highlighted in purple). Trisomy can occur if cells can't properly sort chromosomes during sex-cell formation.

Image by Darryl Leja, National Human Genome Research Institute, National Institutes of Health

Scientists at Fred Hutchinson Cancer Research Center have worked out the molecular underpinnings of how chromosomes make the right number of crossovers — important links that make it possible for developing sex cells (eggs or sperm in humans) to sort those chromosomes properly. Crossovers are a little like Goldilocks’ porridge — they need to be just right. Too few or too many crossovers, and new cells end up with the wrong number of chromosomes, which can cause miscarriages or developmental disorders.

It’s been known for 100 years that our chromosomes have a way of preventing too many crossovers along their length. What’s been missing all that time has been a working model that identifies the key molecules involved.

In work published today in the Proceedings of the National Academy of Sciences, Hutch molecular biologist Dr. Gerry Smith and his team outline just such a model in yeast that explains how chromosomes find their happy medium during sex-cell formation.

“What’s significant is that we’ve developed a molecular model of the proteins involved and how they work together to create crossover interference,” said Smith, the study’s senior author.

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H. pylori test hints at risk factor for stomach cancer

Pilot study suggests specific strain of bacteria may be found more often in East Asian patients with stomach cancer

Sept. 12, 2018 | By Sabrina Richards / Fred Hutch News Service

H. pylori bacterium

Corkscrew-shaped H. pylori bacteria cause a chronic stomach infection and are one of the top risk factors for stomach cancer.

Image courtesy of the Salama Lab / Fred Hutch

Infection with Helicobacter pylori is one of the top risk factors for stomach cancer — but only a small proportion of individuals who carry the bacterium go on to develop cancer. Identifying who is most at risk for cancer will help doctors shape treatment and screening strategies for patients infected with H. pylori.

Now, a pilot study by scientists at Fred Hutchinson Cancer Research Center and Zhengzhou University in China, facilitated by Fred Hutch’s China Initiative, hints that the strain of H. pylori may influence cancer risk. The work, published today in PLOS ONE, shows that patients with stomach cancer are much more likely to be infected with H. pylori that possesses a specific variant of a gene called cagA, which suggests that it may raise the risk of stomach cancer in this region.

“Having the cagA gene has been a marker for cancer and ulcers in Western populations, but in East Asian populations, they all have cagA — it’s not particularly relevant. But in this study we’re saying actually, the type of cagA matters [for cancer risk in East Asia],” said Fred Hutch microbiologist Dr. Nina Salama, the study’s senior author.

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Parsing the deadliness of prostate cancer

Fred Hutch researcher zeroes in on biomarkers to better predict aggressive form of the disease

Sept. 4, 2018 | By Diane Mapes / Fred Hutch News Service

Dr. Janet Stanford

Longtime Fred Hutch epidemiologist and member of the Program in Prostate Cancer Research, Dr. Janet Stanford.

Photo by Robert Hood / Fred Hutch News Service

Biological markers that predict aggressive cancer — that is, the kind that will kill you — have become a bit of a holy grail, especially in prostate cancer.

That’s because these cancers are not all the same. Some are extremely aggressive: They can and do kill, even men in their 40s. Others are slow-growing and only become a concern when they’re detected through preventive screening. These cancers, often referred to as indolent, don’t kill: Men die with them, not of them.

But science hasn’t been able to reliably tease apart which prostate cancer is which, so patients basically roll the decision-making dice with their doctors and choose either invasive treatment, along with its considerable side effects, or active surveillance. As a result, some cancers are overtreated — causing unnecessary suffering to the patient — and others are undertreated, leading to the patient’s death.

Genome-wide association studies (GWAS), i.e., studies that look at the association between genetic variants and a trait or human disease, have identified over 100 inherited variants (or mutations) associated with prostate cancer risk. Other studies are looking at blood, urine and tumor tissue for biological markers that can predict exactly who’s prone to aggressive disease. But many of these biomarkers haven’t been validated through large studies and so are not widely used in the clinic.

Dr. Janet Stanford, a longtime epidemiologist with Fred Hutchinson Cancer Research Center and member of the Program in Prostate Cancer Research, is hoping to change that. 

In late June, her team published the latest in a series of studies pinpointing and then validating a clutch of blood and tumor tissue biomarkers that, she hopes, will in time enable men and their doctors to better predict if a prostate cancer is likely to be lethal or lazy.

“We know there’s a subset of men diagnosed with local-stage prostate cancer who go on to develop and ultimately die of metastatic disease,” she said. “We’re trying to find biomarkers that would tell us how we can better stratify that subset and treat them aggressively and monitor them more closely for early evidence of relapse.”

Stanford’s goal?

“We’re trying find something that has more predictive power than what’s currently available,” she said. “We’ve been trying to develop the tissue biomarkers to be complementary and add value to the Gleason score.”

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Path to a targeted treatment for small-cell lung cancer?

Researchers show how common mutation in SCLC makes mouse tumors more vulnerable to certain cancer drugs

Sept. 4, 2018 | By Sabrina Richards / Fred Hutch News Service

Small-cell lung cancer

An immunohistochemistry image of small-cell lung cancer, with the tumor cells glowing green.

Image courtesy of the MacPherson Lab

Small-cell lung cancer is aggressive and deadly, and progress is long overdue: Patients with SCLC have been treated with the same chemo regimen for 30 years. Could a precision medicine approach deliver patients a much-needed new option? In a new study, scientists at Fred Hutchinson Cancer Research Center reveal how losing a specific gene — which happens in about 15 percent of SCLC patients — accelerates tumor formation in mice. And, most exciting to the researchers, these tumors seem to be uniquely sensitive to a specific drug, which dramatically shrunk some tumors in mice with the mutation.

The drug, known as an HDAC inhibitor, is currently in clinical trials to treat patients with other cancers. The findings “suggest that HDAC inhibitors could have a role in treating small-cell lung cancer if directed to the right subsets of small-cell patients,” said Dr. David MacPherson, a lung cancer researcher and senior author on the study, published today in Cancer Discovery.

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