New Study Finds That Most Cancer Mutations Are Due to Random DNA Copying ‘Mistakes’

Excerpt:

“Johns Hopkins Kimmel Cancer Center scientists report data from a new study providing evidence that random, unpredictable DNA copying ‘mistakes’ account for nearly two-thirds of the mutations that cause cancer. Their research is grounded on a novel mathematical model based on DNA sequencing and epidemiologic data from around the world.

” ‘It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting . But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,’ says Cristian Tomasetti, Ph.D., assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. ‘These copying mistakes are a potent source of cancer that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.’ ”

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Clinical Trial Looks at Targeted Genetic Therapies for Lung Cancer

Excerpt:

“Researchers at the University of Cincinnati (UC) College of Medicine are enrolling patients in a clinical trial looking at targeted gene therapies in patients with early stage lung cancer who have had surgery.

“This could help researchers gain insight into genetic targets that could aid in earlier intervention and better outcomes for patients.

” ‘Despite therapeutic advances in recent years, cancer remains the second leading cause of death in the United States, and effective new therapies are still desperately needed. Additionally, lung cancer is the leading cause of cancer deaths for women and for men,’ says Sandra Starnes, MD, Dr. John B. Flege Jr. Chair in Cardiothoracic Surgery, associate professor of surgery and co-director of the UC Cancer Institute’s Comprehensive Lung Cancer Center. ‘Targeted genetic therapy holds great promise for improved efficacy in treating patients. In this trial, researchers will evaluate the use of a newer targeted therapy for early stage who have had surgery and completed post-operative chemotherapy.’ ”

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Genetic Profile of Treatment-Resistant Lung Cancer More Variable Than Previously Understood

Excerpt:

“The genetic mutations underlying treatment resistance in non-small cell lung cancer (NSCLC) are more complex and dynamic than previously thought. Analysis of 355 biopsied tumors from patients who acquired resistance to EGFR inhibitors, the most common form of targeted therapy for NSCLC, found that mutations frequently varied between biopsies and that nearly one in five patients harbored more than one type of genetic resistance to treatment. Findings will be presented today at the 2017 Multidisciplinary Thoracic Cancers Symposium.”

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New RAF-targeted Therapeutic Shows Early Promise Against Tumors With BRAF and RAS Mutations

Excerpt:

“The new investigational anticancer therapeutic BGB-283, which targets the RAF family of proteins, was safe, tolerable, and showed signs of clinical activity in patients who had a range of types of cancer with mutations in BRAF, KRAS, and NRAS, according to results from a phase I clinical trial presented here at the AACR Annual Meeting 2016, April 16-20.

“ ‘BRAF gene mutations fuel cancer cell proliferation and survival in a number of types of cancer, including melanoma, and thyroid and colorectal cancers,’ said Jayesh Desai, FRACP, a medical oncologist at The Royal Melbourne Hospital in Melbourne, Australia. ‘In melanoma, the BRAF V600E mutation predominates, and specific inhibitors of the BRAF V600E mutant protein have been approved for treating patients with melanoma with BRAF V600E gene mutations.’ ”

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'Liquid Biopsy' Blood Test Detects Genetic Mutations in Common Form of Lung Cancer

Excerpt:

“A simple blood test can rapidly and accurately detect mutations in two key genes in non-small cell lung tumors, researchers at Dana-Farber Cancer Institute and other institutions report in a new study – demonstrating the test’s potential as a clinical tool for identifying patients who can benefit from drugs targeting those mutations.

“The , known as a , proved so reliable in the study that the Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) this week became the first medical facility in the country to offer it to all patients with non-small cell  (NSCLC), either at the time of first diagnosis or of relapse following previous treatment.

“NSCLC is the most common form of lung cancer, diagnosed in more than 200,000 people in the United States each year, according to the American Cancer Society. An estimated 30 percent of NSCLC patients have  in either of the genes included in the study, and can often be treated with targeted therapies. The study is being published online today by the journal JAMA Oncology.”

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NCCN Adds New Gene Mutations to Consider in Women's Cancers

Excerpt:

“The National Comprehensive Cancer Network (NCCN) has added several new genetic mutations to be considered when determining risk-management strategies for hereditary breast and ovarian cancers.

“The recent discovery that the genetic mutation PALB2 is associated with an aggressive form of breast cancer, as well as the realization that the newer ovarian cancer genes RAD51CRAD51D, and BRIP1 pose an added lifetime risk for ovarian cancer, should prompt physicians to discuss possible prophylactic procedures with patients who are found to carry these mutations, Tuya Pal, MD, from the Moffitt Cancer Center, Tampa, Florida, said here at the NCCN 21st Annual Conference.

” ‘Within the past year, more data have emerged regarding these new genes for ovarian cancer risk. In the past, the NCCN recommendation to either recommend or consider risk-reducing salpingo-oophorectomy was limited to the presence of BRCA1BRCA2 and Lynch syndrome,’ Dr Pal told Medscape Medical News.”

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UCSF Center Adds to Revolution of Care for BRCA Carriers

Excerpt:

“A new center at University of California, San Francisco, is designed to provide comprehensive and integrated care for patients with cancer who carry BRCA and other mutations.

“The Center for BRCA Research at UCSF Helen Diller Family Comprehensive Cancer Center joins Basser Center for BRCA in Philadelphia as the only facilities solely devoted to BRCA–related cancers.

“HemOnc Today spoke with Pamela N. Munster, MD, leader of the developmental therapeutics program and co-director of the Center for BRCA Research, about how the center came about, how she became involved, and what she hopes the center will do for BRCA mutation carriers and their families.”

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Blood Test Picks out Prostate Cancer Drug Resistance

“Scientists have developed a blood test that can identify key mutations driving resistance to a widely used prostate cancer drug, and identify in advance patients who will not respond to treatment.

“The new research paves the way for information from a  to inform  in future, with only those  whose cancers are free of resistance mutations taking the drug, abiraterone.

“The study is also a proof of principle that tests for cancer DNA in the bloodstream can be used to detect  – allowing patients who will not benefit from one drug to be given an alternative treatment instead.

“Researchers at The Institute of Cancer Research, London, the Royal Marsden NHS Foundation Trust, and the University of Trento, Italy, analysed 274 blood samples from 97 patients using state-of-the-art DNA sequencing techniques.

“They found that mutations in a gene called the androgen receptor (AR) predicted resistance to the prostate cancer drug abiraterone, and that patients with these mutations had poorer survival.”


Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment

“Multigene testing of women who tested negative for BRCA1 and BRCA2 found some of them harbored other harmful genetic mutations—most commonly, moderate-risk breast and ovarian cancer genes, as well as Lynch syndrome genes (which increase the risk of ovarian cancer)—according to an article by Desmond et al in JAMA Oncology.

“Multigene panel genetic tests are increasingly recommended for patients evaluated for a predisposition to hereditary breast/ovarian cancer. However, the rapid introduction of these tests has raised concerns, because many of the tested genes are low- to moderate-risk genes for which consensus management guidelines have not been introduced or were introduced only very recently, according to the study background.

“Leif W. Ellisen, MD, PhD, of Massachusetts General Hospital Cancer Center, and coauthors wanted to determine how often multigene panel testing would identify mutations that warranted some clinical action among women appropriately tested but lacking BRCA1 and BRCA2 mutations.”