{"id":20475,"date":"2020-02-27T12:00:00","date_gmt":"2020-02-27T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2020\/proteogenomic-core-needle-biopsy-breast"},"modified":"2024-11-03T15:16:49","modified_gmt":"2024-11-03T15:16:49","slug":"new-approach-uses-much-less-tissue-to-analyze-tumor-proteins-and-genes","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/new-approach-uses-much-less-tissue-to-analyze-tumor-proteins-and-genes\/","title":{"rendered":"New Approach Uses Much Less Tissue to Analyze Tumor Proteins and Genes"},"content":{"rendered":"
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An illustration of a\u00a0core needle biopsy. Researchers have developed a way to use tissue from a single core needle biopsy to analyze a tumor\u2019s protein profile and its genetic changes.<\/p>\n

Credit: Courtesy of Mayo Clinic<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Analyzing tumors for genetic changes can provide important information, such as whether a patient is a candidate for a specific targeted therapy<\/a>, and is an important aspect of treatment for a growing number of cancers. But tumor biologists are increasingly coming to understand the value of integrating multiple layers of information beyond DNA changes to understand how tumors function, including more detailed information about the proteins in tumor cells.<\/p>\n

Now, researchers have developed a way to do combined molecular analyses that uses a much smaller amount of tissue<\/a> than has previously been possible. Using this \u201cmicroscaled\u201d approach, the researchers were able to find out why some women with breast cancer responded well to a targeted treatment and others did not.<\/p>\n

This approach could be a step toward bringing the analysis of proteins in tumors, known as proteomics, into cancer care, the study authors believe. Until now, proteomic analysis has required too much tissue to be of immediate clinical utility, but in this study the amount of tissue obtained in single core needle biopsies<\/a>\u00a0was enough to analyze a tumor\u2019s protein profile as well as its genetic changes.<\/p>\n

With core needle biopsies collected from 14 women with HER2-positive<\/a>\u00a0breast cancer both before and just after starting treatment, a research team from Baylor College of Medicine and the Broad Institute was able to explain why 5 of those women did not respond to HER2-targeted therapy while the other 9 did.<\/p>\n

The findings from the NCI-supported study were published January 27 in Nature Communications<\/em>.<\/p>\n

\u201cThis is a very interesting approach,\u201d commented George Sledge, M.D., an oncologist at Stanford University Medical Center who specializes in breast cancer. He expects the approach to draw interest from the wider breast cancer community, especially if it is validated in a larger group of patients across multiple medical centers.<\/p>\n

The Business End of the Genome<\/h2>\n

Cancer is often described as a disease of the genome, meaning that cancer is caused by changes in DNA. The genome provides the instructions for making proteins, and it is proteins that control cell growth and are typically the target of precision drugs.<\/p>\n

\u201cProteins are the business end of the genome, carrying out nearly all key functions in cells, including in cancer cells,\u201d said one of the study investigators, Steven Carr, Ph.D., the senior director of proteomics research at the Broad Institute. But there hasn\u2019t been a way to globally measure proteins and the chemical changes that affect their behavior in a test that could be applied in a clinical setting.<\/p>\n

Many types of genetic tests<\/a> are already being used in the clinic. For example, many targeted therapies have what are known as \u201ccompanion diagnostics\u201d that are approved to identify the specific genetic alterations in tumors that those drugs act on. And the Food and Drug Administration has approved more comprehensive genomic assays, which Dr. Sledge said are increasingly being used to analyze metastatic cancers.<\/p>\n

\u201cThe vast majority of drugs go after proteins. To directly analyze the molecule that you\u2019re targeting would be the most effective way to tell if a drug will be effective,\u201d said Henry Rodriguez, Ph.D., director of NCI\u2019s Office of Cancer Clinical Proteomics Research<\/a> (OCCPR). The OCCPR oversees the Clinical Proteomic Tumor Analysis Consortium<\/a>, of which the Baylor and Broad teams are members.<\/p>\n

Developing a \u201cMicroscaled Proteogenomics Pipeline\u201d<\/h2>\n

Until now, joint analysis of proteins and genetic changes, known as proteogenomics<\/a>, required \u201cdime-sized pieces of tumor\u201d that were removed during surgery, explained Matthew Ellis, M.D., Ph.D., director of the Lester and Sue Smith Breast Center at Baylor.<\/p>\n

By contrast, core needle biopsies are collected in an outpatient setting, earlier in a patient\u2019s care than surgery, to help make a diagnosis and to direct the initial course of therapy. Core needle biopsies contain much less tissue than is removed during surgery, so researchers at Broad and Baylor developed techniques to obtain similar information from these much smaller samples.<\/p>\n

When doing proteogenomic analysis on surgical samples, the tissue is typically frozen and then pulverized into powder so that uniform material can be used for DNA, RNA, and protein analysis, explained Shankha Satpathy, Ph.D., of the Broad Institute and member of the study team. But there is not enough tissue in core biopsies to take that approach. Instead, to analyze uniform samples, the needle biopsy tissue was carved into thin slices, which were then shuffled to uniformly mix the slices.<\/p>\n

To be able to extract as much information as possible from so little material, the researchers extracted both DNA and protein simultaneously and then labeled proteins in a way that made them easier to detect and classify in a device known as a mass spectrometer. They also combined protein samples in a way that allowed for accurate comparison between samples, the researchers reported.<\/p>\n

To be useful in clinical practice, proteogenomic analysis needs to make efficient use of time as well as tissue. Currently, genomic analysis takes 2 to 3 weeks, Dr. Sledge says. The wait can be wrenching for patients, but \u201cthe delay is worthwhile if it gives more definitive information and a more nuanced look at treatment options,\u201d he said.<\/p>\n

Dr. Carr said he is hopeful that with further development, these proteogenomic techniques will deliver genomic and proteomic results in a similar time frame as genomics alone.<\/p>\n

Proof of Concept: HER2-Positive Breast Cancer<\/h2>\n

To see how their refashioned approach for proteogenomic analysis might work in a real-world situation, the researchers tested it on tumor samples from women diagnosed with HER2-positive breast cancer who were undergoing treatment with trastuzumab (Herceptin)<\/a>, an antibody that works by binding to HER2 proteins and blocking them from working.<\/p>\n

At least one-fifth of patients diagnosed with HER2-positive breast cancer do not adequately respond to trastuzumab, Dr. Ellis explained. Being able to figure out who these patients are would be of great value. Trastuzumab is expensive and can have serious side effects. Plus, giving patients drugs they don\u2019t respond to delays the use of treatments that may be more helpful, he added.<\/p>\n

The researchers analyzed core needle biopsy samples taken from a small number of women with HER2-positive breast cancer both before treatment and again 48\u201272 hours after trastuzumab treatment was initiated. The researchers found that, with proteogenomic analysis, they were able to explain why some patients responded to the drug and others did not.<\/p>\n

In all nine patients who responded to treatment, the researchers found that HER2 protein activity levels were lower after treatment started than before treatment. Among the five patients who didn\u2019t respond, proteogenomics provided important clues as to why. \u201cFor example, in two cases, although the tumor cells had HER2 amplification, they had low HER2 protein expression<\/a>, suggesting a false-positive clinical test,\u201d Dr. Satpathy explained.<\/p>\n

Another patient\u2019s tumor did have high levels of HER2 expression, but it also overexpressed mucin, a protein that coats cell surfaces and that may block trastuzumab from binding to HER2 on cancer cells.<\/p>\n

Further analysis of that patient\u2019s tumor showed elevated activity of a protein called mTOR<\/a>. In laboratory tests of breast cancer cells that overexpress<\/a> mucin and HER2 proteins, combining trastuzumab with everolimus (Afinitor)<\/a>, a drug that targets mTOR, successfully killed the cells.<\/p>\n

\u201cIn the era of targeted therapy, it is critical to know that a therapy is the right choice and is going to be effective,\u201d Dr. Ellis said.<\/p>\n

\u201cThese data are in the HER2-positive population, but there is no reason why this proteogenomic analysis approach can\u2019t be applied to others,\u201d Dr. Sledge said, such as women with triple-negative breast cancer<\/a> and potentially other cancers.<\/p>\n

Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"

February 27, 2020, by NCI Staff An illustration of a\u00a0core needle biopsy. Researchers have developed a way to use tissue from a single core needle biopsy to analyze a tumor\u2019s protein profile and its genetic changes. Credit: Courtesy of Mayo Clinic Analyzing tumors for genetic changes can provide important information, such as whether a patient […]<\/p>\n","protected":false},"author":2,"featured_media":20476,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-20475","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/20475","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=20475"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/20475\/revisions"}],"predecessor-version":[{"id":45680,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/20475\/revisions\/45680"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/20476"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=20475"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=20475"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=20475"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}