{"id":6610,"date":"2019-05-28T16:00:00","date_gmt":"2019-05-28T16:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2019\/proteogenomics-cptac-colon-cancer"},"modified":"2024-11-03T15:17:12","modified_gmt":"2024-11-03T15:17:12","slug":"studying-genes-and-proteins-together-sheds-new-light-on-colon-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/studying-genes-and-proteins-together-sheds-new-light-on-colon-cancer\/","title":{"rendered":"Studying Genes and Proteins Together Sheds New Light on Colon Cancer"},"content":{"rendered":"

May 28, 2019, by NCI Staff<\/p>\n

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Researchers have\u00a0identified proteins that are different in cancer cells and may be exploited for several purposes, including as potential targets for new cancer drugs.<\/p>\n

Credit: Adapted from Cell May 2019. doi: 10.1016\/j.cell.2019.03.030. CC BY-NC-ND 4.0<\/p>\n<\/div>\n<\/figcaption><\/figure>\n

By combining the study of genes<\/a> and proteins<\/a> in human colon cancer<\/a> tumors, scientists have discovered new features of the disease that they believe have the potential to guide novel treatment strategies.<\/p>\n

The integrated study of genes and proteins, called proteogenomics<\/a>, is a fairly new area of research intended to provide researchers with a greater understanding of biology\u2014one that cannot be gained by studying genes alone.<\/p>\n

The scientists scoured the gene and protein \u201cprofiles\u201d of colon tumors from more than 100 people, identifying several proteins that appear to drive colon cancer growth<\/a> and could be potential drug targets.<\/p>\n

The study, published May 2 in Cell<\/em>, was led by members of NCI\u2019s Clinical Proteomic Tumor Analysis Consortium (CPTAC)<\/a>, a collaborative effort to \u201cdiscover major cancer-causing proteogenomic alterations\u201d in several cancer types, said Henry Rodriguez, Ph.D., director of NCI\u2019s Office of Cancer Clinical Proteomics Research<\/a>.<\/p>\n

In 2014, the CPTAC team completed the first large-scale proteogenomic study of colon cancer<\/a>, which zeroed in on the basic characteristics of colon tumors.<\/p>\n

\u201cA major focus of this new study was: Can we use proteogenomic integration to guide therapies?\u201d said lead investigator Bing Zhang, Ph.D., of Baylor College of Medicine in Houston.<\/p>\n

Why Study Proteins?<\/h2>\n

There\u2019s no doubt that studying genes has revealed a trove of information about cancer biology. For example, scientists have used genetic<\/a> data from tumors to predict how DNA<\/a> changes may affect cancer cell behavior, such as uncontrolled growth.<\/p>\n

But DNA gives rise to RNA, which then generates proteins<\/a>, and proteins are what actually drive cell behavior, Dr. Zhang noted.<\/p>\n

One important caveat of genetic studies is that the jump from genetic data to cell behavior isn\u2019t always straightforward because \u201cgenetic mutations<\/a> do not always result in the predicted change in the corresponding protein,\u201d Dr. Rodriguez explained. \u201cAnd there are many other factors that influence protein activity and contribute to tumor behavior.\u201d<\/p>\n

In addition, studies have found that DNA and RNA data are not \u201csufficient, on their own, to dictate the optimal choice of anti-cancer agents with which to treat a particular patient\u2019s tumor in most cases,\u201d wrote Jung-Kuei Chen, Ph.D., and Michael Yaffe, M.D., Ph.D., of the Koch Institute for Integrative Cancer Research at MIT\u00a0in an accompanying commentary<\/a> in Cell<\/em>.<\/p>\n

What\u2019s more, the vast majority of cancer drugs target proteins, not genes, Dr. Zhang noted, so protein studies may be best suited to identify new drug targets.<\/p>\n

But until recently, large-scale protein studies (called proteomic<\/a> studies) had not been possible because \u201cproteomic technology lagged behind genomic<\/a> technology,\u201d he explained.<\/p>\n

CPTAC was formed in 2011 to apply new advances in technology and computational approaches to the study of cancer. Based on the success of CPTAC\u2019s pilot studies, the initiative was later expanded. \u201cThis new study is a result of that expansion,\u201d Dr. Rodriguez said.<\/p>\n

A New Understanding of Colon Cancer<\/h2>\n

The CPTAC team began by collecting samples of blood, tumor tissue, and nearby normal tissue from 110 people with colon cancer.<\/p>\n

They then captured the sequences of all DNA, RNA, microRNA<\/a>, and protein molecules in each sample. In addition, they looked at how many copies of each gene were present (gene copy number), the relative amounts of each protein (protein expression<\/a>), and whether the proteins were chemically modified (protein phosphorylation<\/a>).<\/p>\n

After using computational approaches to merge these data, the team compared the \u201cmolecular profiles\u201d of the participants\u2019 tumor tissue with that of their healthy tissue.<\/p>\n

Although they identified thousands of differences, certain findings jumped out.<\/p>\n

For example, a protein called RB1 is known to keep cell growth in check. The gene for RB1 tends to be deleted in many cancer types, but colon tumors often have more copies of the gene than normal. Why colon cancer cells would have more of a protein that prevents cell growth has baffled scientists for years.<\/p>\n

When the CPTAC researchers analyzed their data, an answer became clear: In these colon cancer samples, the RB1 protein was chemically modified in a way that stopped it from controlling cell growth. The data also suggested that this modified RB1 may block a type of cell suicide, called apoptosis<\/a>, providing another advantage to cancer cells.<\/p>\n

What\u2019s more, the team found evidence that an enzyme named CDK2 was likely responsible for chemically modifying RB1. Because drugs that block CDK2 activity are already available, it\u2019s possible that such drugs could work for people with colon cancer, the authors noted.<\/p>\n

An Idea to Improve Immunotherapy\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/h2>\n

The investigators made another interesting finding regarding a subtype of colon cancer called microsatellite instability<\/a> high (MSI-H). About 20% of people with colon cancer have MSI-H tumors.<\/p>\n

The immunotherapy<\/a> drug pembrolizumab (Keytruda)<\/a> is approved by the Food and Drug Administration to treat some patients with MSI-H colon cancer<\/a>, but it doesn\u2019t work for about 60% of such patients and scientists have been trying to understand why.<\/p>\n

The team found that, compared with tumors that were not MSI-H, some MSI-H colon tumors had higher amounts of enzymes<\/a> that control glycolysis<\/a>, a method that cells use to create energy. What\u2019s more, MSI-H tumors with high levels of those enzymes had very few cancer-killing immune cells<\/a>. Without immune cells in the tumor, an immunotherapy is not likely to work, Dr. Zhang explained.<\/p>\n

This surprising relationship between glycolysis and immune cells raises the possibility of a new approach for patients with MSI-H colon cancer that is immunotherapy-resistant, the authors stated.<\/p>\n

More to Explore<\/h2>\n

While the CPTAC team has found some interesting connections, there\u2019s still a mountain of data to explore, Dr. Zhang pointed out.<\/p>\n

This study \u201cpresents several clearly testable hypotheses and serves as a valuable colon cancer resource for further focused interrogation,\u201d Drs. Chen and Yaffe wrote.<\/p>\n

To enable future investigations, data from this and other CPTAC studies are available to the public for free<\/a> (subject to a\u00a0data use agreement), Dr. Rodriguez explained. In fact, more than 19,000 people have used the database to date.\u00a0<\/p>\n

Sharing data \u201callows a wider group of scientists to replicate [CPTAC\u2019s findings] and, importantly, extend and accelerate research in unanticipated directions,\u201d he said.<\/p>\n

And colon cancer isn\u2019t CPTAC\u2019s only focus. They\u2019ve also completed proteogenomic studies of breast, ovarian, endometrial, and kidney cancer and plan to finish studies of three additional cancer types in the coming years, Dr. Rodriguez noted.<\/p>\n

If that seems like a lot of work, that\u2019s because it is.<\/p>\n

\u201cThe teamwork [within CPTAC] is what makes this happen,\u201d Dr. Zhang emphasized. \u201cThe power of this consortium is that it brings investigators with expertise in different areas together to address challenging questions,\u201d he added.<\/p>\n

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

May 28, 2019, by NCI Staff Researchers have\u00a0identified proteins that are different in cancer cells and may be exploited for several purposes, including as potential targets for new cancer drugs. Credit: Adapted from Cell May 2019. doi: 10.1016\/j.cell.2019.03.030. CC BY-NC-ND 4.0 By combining the study of genes and proteins in human colon cancer tumors, scientists […]<\/p>\n","protected":false},"author":2,"featured_media":6611,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-6610","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\/6610","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=6610"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/6610\/revisions"}],"predecessor-version":[{"id":44501,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/6610\/revisions\/44501"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/6611"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=6610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=6610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=6610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}