Transforming Cancer Research – When it comes to cancer care, it’s clear that a one-size-fits-all model doesn’t fit. Today, armed with increasing data from genetic research, physician-scientists are introducing a new era of personalized cancer care. The ultimate goal: to make cancer a manageable, if not curable, disease.
Cancer is not one disease; It comes in many forms throughout the body, and no two patients are alike. That’s a big challenge for doctors trying to choose the best treatment for each patient and researchers working to develop better methods of care.
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For answers, physician-scientists at the University of Washington are turning to the genetic code. Conducting one of the world’s largest research efforts of its kind, they are gaining a strong understanding of the roots of cancer and are applying that knowledge to customize treatment based on the genetic signature of each tumor – a process known as individualization.
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“Cancer care is undergoing a major transformation,” said Timothy Eberlein, MD, director of the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “Providing effective treatment, tailored to each patient based on their unique situation is the ultimate goal.”
Individuality is based on our growing understanding of DNA, the material in all human cells that guides development and growth throughout life. Our genes are functional units of DNA; The collection of all genetic material is called the genome. Genomics tries to understand how genes interact with each other and the environment in ways related to health and disease.
DNA mutations, genetic code abnormalities that are inherited or caused by environmental factors, can accelerate cell division and eventually lead to cancer. Scientists study the differences between the DNA of normal cells and cancer cells to find mutations that cause cancer, find out what causes it, and determine how to stop it.
Major technological advances in recent years—many of which have been made at the University of Washington’s famous Genome Institute—have made genome analysis much faster and more economical, fueling research on the fundamentals. genetics of the disease.
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Sequencing the cancer genome was pioneered by a group of researchers at the Genome Institute. In 2008, they tested the first ever genome of a cancer patient, an individual with acute myeloid leukemia (AML). A subsequent study at the University of Washington in 2013, involving some 200 patients and approximately 150 researchers, revealed almost all the major changes in AML.
University of Washington oncologist Timothy Ley, MD, led the first team to fully sequence an entire cancer genome from a patient with acute myeloid leukemia (AML).
“We now have the genetic playbook for this type of leukemia,” said study co-author Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology. “This information can help us begin to understand which patients need more aggressive treatment up front and can be treated more effectively with standard chemotherapy.”
The garden continues to mushroom, to the University of Washington and beyond. Scientists at the Genome Institute, working with Siteman oncologists, have conducted similar studies on breast, ovarian, lung, uterine and other cancers. And the work is starting to go into the clinic; The University of Washington Genomics and Pathology Services (GPS@WUSTL) now publicly offers testing for 42 known genetic mutations in cancer—information doctors can use to improve treatment, said Jon Heusel, MD, PhD. , GPS@WUSTL chief medical officer and medical director of Genomic Testing for Clinical Research at the Genome Institute.
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“GPS@WUSTL brings the promise of human genomics to the clinic,” said Karen Seibert, PhD, its director. “We use the latest gene sequencing technology and refer to the results of known treatment options for patient-specific mutations. In addition to patient care, our laboratories support clinical trials designed to identify new methods of treatment. diagnosed and treated.”
Ongoing research is changing the way tumor type definitions are used to inform treatment choices. The work is traditionally done by looking at cells under a microscope; but classifying some tumors in this way is difficult, and pathologists do not always agree. Genetic testing provides a more detailed picture, allowing doctors to classify tumors based on their genetic signatures in addition to their location in the body. According to previous clinical studies, the results may change the course of treatment for some patients.
A recent study on endometrial cancer is a case in point. Clinically, endometrial cancer, found in the lining of the uterus, occurs in two types, one more serious than the other. In a genetic analysis of tumor samples from 373 women with endometrial cancer, researchers discovered four new types of tumors. What’s more, one of the subtypes, identified as a less severe form through pathology tests alone, is actually similar to the more severe type and requires more intensive treatment.
Elaine Mardis, PhD, is director of the Genome Institute at the University of Washington. She is using genomic analysis techniques to study cancer.
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“We’re entering an era where tumors can be evaluated by genomics, not just by looking at cancer cells under a microscope,” said Elaine Mardis, PhD, director of the Genome Institute and project leader. “This comprehensive approach provides a clear idea of how endometrial cancer in particular will behave and will be important for gynecological oncologists who treat this disease.”
This type of test has already proven beneficial for breast cancer – a type of cancer that is on the personal front line. In one study of 77 postmenopausal women with an early stage of the disease, Mardis and colleagues identified distinct genetic signatures that accurately predicted which patients were most likely to benefit from weight-loss drugs. estrogen. Medicines can reduce the size of breast tumors, making it easier for many women to get breast-conserving surgery instead of mastectomy.
“This is one of the first cancer genomics studies to use mutations to predict response to treatment,” said Mardis, the lead researcher. “If our results are validated in larger studies, we think that genomic information will be one additional data point that doctors consider when choosing several treatment options for their patients.”
The Siteman Cancer Center coordinates patient enrollment in clinical trials, where access to experimental treatments like this one is available for many types of cancer. These tests are the key to learning about useful tests and treatments and should be common care.
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Surprisingly, some studies show genetic kinship among tumors in different parts of the body, and the effect is far-reaching. The Mardis endometrial cancer study showed that some endometrial cancers are genetically similar to deadly types of ovarian cancer and breast cancer-like. In patients with breast cancer, researchers found many genetic changes not previously associated with breast tumors but known in patients with leukemia and prostate, colon, lung, skin and other cancers. Patients with these mutations may benefit from drugs that have previously been used for certain types of cancer.
In another study, researchers at the University of Washington found that some women with HER2-positive breast cancer can benefit from anti-HER2 drugs even though conventional tests do not show that they are candidates for the drugs. The study shows the potential value of testing even one gene of interest, said Ron Bose, MD, PhD, an oncologist at Washington University Barnes-Jewish Hospital.
“If we can identify changes that we can act on, that information will help us better guide treatment,” he said. “In this case, we don’t even have to develop new drugs against HER2 mutations. It’s a matter of availability to patients.”
Gene sequencing may also help map the genetic progression of a person’s disease. Like bacteria, whose habit of constantly changing can make them resistant to antibiotics, tumors are also constantly changing, including the response to treatment. Genetic surveillance may allow doctors to monitor a patient’s response to treatment and signal when it’s time to try a different approach.
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“Already, we can treat these patients more effectively and use the word ‘cure’ more often,” said Ryan Fields, MD, a Washington University surgeon at Barnes-Jewish Hospital and a member of the Siteman Cancer Center. . “But even if we don’t use the word ‘cure’, we’re turning cancer into a more chronic disease, so it’s more like high blood pressure or high cholesterol – something that can be managed over time in different ways, improving treatment but also and improving the patient’s quality of life.”
Solid tumors: brain, breast, colon, stromal gastrointestinal, head and neck, liver and biliary structures, lung, ovary, spleen, prostate, skin, thymic, uterus and many others
The results may, but do not always, suggest targeted therapy based on the patient’s genes. Request the services of your doctor. Many insurance plans cover the cost.
At the Siteman Cancer Center, patients can talk with counselors about hereditary cancer risk and genetic mutations identified through screening.
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The American Society of Clinical Oncology suggests that patients ask their doctors the following questions to learn more about personal availability:
Ellis, MJ, Ding L, Shen D, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER. Genome-wide analysis informs grapevine response to aromatase inhibition.
Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. HER2 mutational activity of the HER2 gene in the development of malignant breast cancer. These research scientists actually grow small tumors from cancer patients.
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