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October 2006 Posts
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Minnesota Gene Pool Blog

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October 31, 2006

Survivorship, Family History and Inherited Susceptibility for Cancer

The New York Times has a moving and personal essay (In Breast Cancer, There Is a Single Agenda: Stay Alive, New York Times, October 31, 2006) by Aliyah Barukin today where she reflects on her journey through cancer diagnosis, treatment and survivorship. Last but not least, because of being half Ashkenazi Jewish, she describes the experience having and receiving genetic testing results for BRCA1 and BRCA2 mutations.

I will not be a spoiler and reveal how the story ends, but Ms. Barukin's reflections made me think of a conversation I had with a colleague who worked in the Cancer Control Division at CDC who made the connection between inherited susceptibility for cancer and survivorship. In all cases, the story starts with the person with cancer, but quickly radiates to other family members. In both cases, the threat of an untimely end of life heightens sensations, fears, and feelings of vulnerability in both the person with cancer and those closest to her. In both cases, the consequences of the disease cross generations, both in terms of guilt of passing on the increased risk for cancer and the guilt of leaving children behind without a parent. In both cases, there is the need to learn to live with the very real specter of cancer recurring (or occurring) and the real threat of untimely illness and death that family members share.

When it comes to our health and wellbeing, we all are only one step away from disaster at any time. One false step, one moment of inattention behind the wheel, one wrong move that results in serious injury can bring lifechanging circumstances for us and our families. However, for most of us, we learn to delude ourselves that the abyss is not really there, that these horrific events will only happen to someone else. For those who have had cancer or have an inherited predisposition to cancer, that comforting delusion is shattered and cannot be easily recovered and they must learn to live with the knowledge of the tenuous nature of good health. In these ways--and probably others--the knowledge of an inherited susceptiblity for cancer and surviving a cancer diagnosis are similar.


New Genomic Tests Guide Choice of Chemotherapy in Cancer Patients

DURHAM, N.C. – Scientists at Duke University's Institute for Genome Sciences & Policy have developed a panel of genomic tests that analyzes the unique molecular traits of a cancerous tumor and determines which chemotherapy will most aggressively attack that patient's cancer.

In experiments reported in the November 2006 issue of the journal Nature Medicine, the researchers applied the genomic tests to cells derived from tumors of cancer patients. They found that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor.

The Duke team plans to begin a clinical trial of the genomic tests in breast cancer patients next year.

DURHAM, N.C. – Scientists at Duke University's Institute for Genome Sciences & Policy have developed a panel of genomic tests that analyzes the unique molecular traits of a cancerous tumor and determines which chemotherapy will most aggressively attack that patient's cancer.

In experiments reported in the November 2006 issue of the journal Nature Medicine, the researchers applied the genomic tests to cells derived from tumors of cancer patients. They found that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor.

The Duke team plans to begin a clinical trial of the genomic tests in breast cancer patients next year.

The new tests have the potential to save lives and reduce patients' exposure to the toxic side effects of chemotherapy, said Anil Potti, M.D., the study's lead investigator and an assistant professor of medicine in the Duke Institute for Genome Sciences & Policy. The tests are designed to help doctors select and initiate treatment with the best drug for a patient's tumor instead of trying various drugs in succession until the right one is found, Potti said.

"Over 400,000 patients in the United States are treated with chemotherapy each year, without a firm basis for which drug they receive," said Joseph Nevins, Ph.D., the study's senior investigator and a professor of genetics at the Duke Institute for Genome Sciences & Policy. "We believe these genomic tests have the potential to revolutionize cancer care by identifying the right drug for each individual patient."

The tests work by scanning thousands of genes from a patient's tumor to produce a "genomic" profile of the tumor's molecular makeup. Using the genomic tests in cancer cells in the laboratory, the scientists successfully matched the right chemotherapy for the patient's tumor type. The scientists were then able to validate their predictions against patients' actual clinical outcomes.

Doctors currently must use a trial-and-error approach to chemotherapy, trying various established drugs to see which has an effect. As a result, patients often undergo multiple toxic therapies in a process that places patients' lives at risk as their conditions worsen with each treatment.

"Chemotherapy will likely continue to be the backbone of many anticancer treatment strategies," said Potti. "With the new test, we think that physicians will be able to personalize chemotherapy in a way that should improve outcomes."

The first clinical trial will compare how well patients respond to chemotherapy when it is guided by the new genomic predictors versus when it is selected by physicians in the usual trial-and-error manner. The researchers anticipate that they will enroll approximately 120 patients with breast cancer in the study. Subsequent clinical trials will enroll hundreds of patients with lung and ovarian cancer, Potti said.

If proven effective, the tests could be applied to all cancers in which chemotherapy is given, not just breast, lung, and ovarian cancer, Potti said.

The researchers developed the new tests through a process that included analyzing the activity of thousands of genes in cells taken from the tumors of cancer patients.

In using the test, scientists extract the genetic molecule "messenger RNA" from a cancer patient's tumor cells. Messenger RNA translates a gene's DNA code into proteins that run the cell's activities. Hence, it is a barometer of a gene's activity level inside the cell.

The scientists then label the messenger RNA with fluorescent tags and place the labeled molecules on a tiny glass slide, called a gene chip, which binds to segments of DNA representing the tens of thousands of genes in the genome.

When scanned with special light, the fluorescent RNA emits a telltale luminescence that demonstrates how much RNA is present on the chip, and this reading indicates which genes are most active in a given tumor. The scientists use this signature of gene expression in the cancer cells to predict which chemotherapeutic agent will be most powerful in treating the specific tumor.

In the current study, funded by the National Institutes of Health, the researchers assessed the tests' ability to predict how patients with breast and ovarian cancer and leukemia responded to various anticancer drugs. They found that the tests predicted the clinical response to chemotherapy with 80 percent accuracy.

"Importantly, we believe this research can improve the efficiency of chemotherapy without changing the drugs currently used in standard practice," Nevins said. "Rather, the tests simply provide an approach to better selection, within a repertoire of available drugs."

Other researchers participating in the study included Holly K. Dressman, Andrea Bild, Jeffrey Marks, Andrew Berchuck, Geoffrey S. Ginsburg and Phillip Febbo of the Duke Institute for Genome Sciences & Policy; Richard F. Riedel, Robyn Sayer, Janiel Cragun, Michael J. Kelley, Rebecca Peterson, and David Harpole of Duke University Medical Center; and Gina Chan, Hope Cottrill and Johnathan Lancaster of the H. Lee Moffitt Cancer Center in Tampa, Fl.

Source: http://www.mc.duke.edu