DNA Mutations Shed in Blood Predicts Response to Immunotherapy in Patients With Cancer

Excerpt:

“In a first-of-its-kind study, University of California San Diego School of Medicine researchers report that a blood sample, or liquid biopsy, can reveal which patients will respond to checkpoint inhibitor-based immunotherapies.

” ‘We can help predict response to immunotherapy by measuring the number of mutations in circulating tumor DNA using a simple blood test,’ said Yulian Khagi, MD, UC San Diego Moores Cancer Center fellow and first author. ‘Immunotherapy can result in serious side effects, and therefore being able to predict who will respond is important to mitigating potential risk to each patient.’ ”

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Liquid Biopsies for Identification of EGFR Mutations and Prediction of Recurrence

Excerpt:

“Three manuscripts published in the recent issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), explored the versatility of liquid biopsies by identifying EGFR mutations using circulating tumor DNA (ctDNA) in urine and plasma and examining circulating tumor cells (CTCs) in plasma to predict the risk of lung cancer recurrence after surgical resection. Collectively, these findings illustrate the potential and reach of liquid biopsies in both identifying patients suitable for targeted treatment as well as predicting cancer recurrence.

“Lung cancer is the most common type of cancer with the highest cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancer and most patients present with advanced disease at diagnosis. Surgical resection is the preferred treatment option for patients with medically operable tumors. However, disease recurrence occurs in approximately 50% of cases. Patients with advanced disease are often not candidates for surgical resection and commonly harbor driver mutations that can be targeted by drugs. A major challenge for assessing driver mutations, such as epidermal growth factor receptor (EGFR) mutations, in advanced disease is the scarcity of suitable biopsy tissue for molecular testing. A minimally invasive alternative to invasive tissue biopsy is the use of liquid biopsy, which analyzes ctDNA or CTCs in a liquid biological sample (i.e. urine, blood, or serum).”

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Can Liquid Biopsies and Tumor Biomarkers Personalize Prostate Cancer Treatment?

Excerpt:

“Experimental, minimally invasive ‘liquid biopsy’ blood tests might soon help to personalize prostate cancer treatment by predicting androgen resistance and survival benefits from particular treatments, researchers announced at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

“Liquid biopsies detect circulating tumor cells (CTCs) or bits of tumor DNA (ctDNA). Not all tumors shed cells or DNA into a patient’s bloodstreams, but most do. And when they do, they can reveal a lot about themselves—including molecular signatures that can be targeted with specific treatments.

“Recent years have seen an explosion of candidate biomarkers for prostate cancer and other malignancies, including both liquid biopsies and tumor-sample gene panels. Most candidate biomarkers have been prognostic gene-mutation signatures that can estimate patient survival regardless of what treatment strategies are attempted. These prognostic tests can be useful for risk-stratifying patients who are participating in clinical studies, or in communicating prognosis to a patient and his loved ones.”

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Blood Test Predicts Success of Neuroendocrine Cancer Therapy

Excerpt:

“Malignant neuroendocrine tumors (NETs) are relatively rare, notoriously difficult to treat, and associated with poor long-term survival. According to research presented at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an investigative blood test could predict how patients will respond to peptide receptor radionuclide therapy (PRRT) before they commit to a course of treatment.

“Cancerous NETs can develop in a variety of places where hormone signaling occurs between nerve cells and organs of the endocrine system, but the most common origins of these tumors are in the gastrointestinal tract, the lungs and the pancreas. These cancers sneak up on oncologists due to their rarity and the fact that symptoms such as flushing, diarrhea and sweating are often regarded as unrelated to disease and part of normal life events. Most cases are not caught until these tumors have already spread to other organs, making them difficult to treat with conventional means. A targeted treatment established in the early 2000s called peptide receptor radionuclide therapy (PRRT) zeros in on active peptide receptors that are over-expressed on the surface of NETs. The injected drug binds specifically to these receptors and knocks out tumors by irradiating them with a powerful dose of short-range radioactive material while sparing healthy tissues nearby.”

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Black Women Less Likely to Pursue BRCA Testing and Cancer Risk Reduction Measures

Excerpt:

“Findings from a population-based study reported at the 2016 ASCO Annual Meeting revealed that young black women with breast cancer are much less likely to undergo testing for the BRCA gene than other women. Or, if they do carry a BRCA mutation, they are less likely to get a prophylactic mastectomy or salpingo-oophorectomy to reduce the risk of developing cancer.

“The research identified disparities in recipients of BRCA testing between non-Hispanic white women, Hispanic, and black women, with the latter being the least likely to undergo testing. Likewise, black women who were BRCA carriers were less likely to undergo risk-management practices compared with their white and Hispanic counterparts.

“ ‘We need to understand the reasons for these findings,’ said lead study author Tuya Pal, MD, a clinical geneticist at the Moffitt Cancer Center in Tampa, Florida. Ultimately, it’s the patient who must decide whether to have genetic testing and take prophylactic measures for risk management, Pal said.”

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HER2-Enriched Molecular Subgroup Highly Sensitive to Breast Cancer Regimens

“The primary analysis of the phase III CALGB 40601 trial found that pathologic complete response (pCR) to dual HER2 blockade was not statistically higher than anti-HER2 monotherapy. However, there was a high level of intertumoral heterogeneity, and patients with the HER2-enriched subtype had a high pCR with both single and dual anti-HER2 therapy, according to data recently published in the Journal of Clinical Oncology.

“ ‘This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer, and may allow us to take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments and to have a good prognosis,’ said lead study author Lisa Carey, MD, a UNC Lineberger member, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at the University of North Carolina School of Medicine, and the physician-in-chief of the North Carolina Cancer Hospital, in a statement.”


Greater MET/CEP7 Expression May Predict Therapy Response in NSCLC

“Patients with non–small cell lung cancer who had higher MET positivity appeared less likely to harbor other cancer drivers, according to study results.

“Thus, a greater MET/CEP7 ratio — or a comparison of the MET copy number to the number of chromosome 7 centromeres — may predict benefit from treatment with crizotinib (Xalkori, Pfizer) in patients with NSCLC.

“ ‘Generally, there are two ways that the number of copies of the MET gene can be increased: the tumor can make multiple copies of the entire chromosome on which it sits — chromosome 7 — or it can amplify just the MET region,’ Sinead A. Noonan, MD, senior thoracic oncology fellow at University of Colorado School of Medicine, said in a press release. ‘In the first case, MET is unlikely to be the specific driver of the cancer’s biology. But if the MET region is amplified separate from the rest of the chromosome, this should suggest that the MET gene is indeed the area of specific importance to the cancer.’ “


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.”


Gene Mutation Signals Poor Prognosis for Pancreatic Tumors

“For patients with pancreatic neuroendocrine tumors, the presence of recently identified mutations in two key genes is a prognostic factor for poor outcome, researchers report.

” ‘We found loss of nuclear expression in about 23% of the tumors that we studied, and this loss of expression was associated with worse tumors from the outset,’ lead investigator Michelle Heayn, MD, a second-year pathology resident at the University of Pittsburgh Medical Center, told Medscape Medical News.

“Pancreatic tumors with neuroendocrine histology frequently respond to chemotherapy and have a more favorable prognosis than the more common pancreatic adenocarcinomas. However, the mutations are associated with worse disease-free and disease-specific survival.”