Cancer Cell Map Initiative reveals protein interactions that drive cancer

Source: www.scienceboard.net Author: Leah Sherwood, The Science Advisory Board assistant editor A research group has mapped previously unknown interactions between proteins that drive cancer, thereby revealing potential new biomarkers and drug targets. The findings were published in a trio of papers in Science on October 1. The research is the work of the Cancer Cell Map Initiative (CCMI), a multi-institution research program founded in 2015 at the University of California, San Diego (UCSD) and San Francisco (UCSF) campuses. From the gene level to the protein level The CCMI approach seeks to gain a more expansive view of the activity underlying cancer by zooming in from the gene level to the protein level, which is far more detailed. "This is an entirely new way to do cancer research," Nevan Krogan, PhD, director of UCSF's Quantitative Biosciences Institute and co-senior author of the papers, said in a statement. "We realized we need another way to look at cancer that takes it a step beyond DNA." Genes contain instructions for building proteins, which then interact with other proteins. When gene mutations cause disruptions, they are reflected in the interactions among protein complexes that regulate activities in the body or turn individual functions on or off. For example, if a gene mutation results in misshapen protein, it may not interact correctly with other proteins, causing a loss of function that, in some cases, can lead to cancer. "We're elevating the conversation about cancer from individual genes to proteins, allowing us to look at how [...]

Study finds major anti-inflammatory immune activity that favors oral cancer tumors

Source: medicalxpress.com Author: MELISA Institute A collaborative research led by immunologist Estefania Nova-Lamperti from the Universidad de Concepción (Chile), with a branch of researchers from MELISA Institute and other international academic centers, made progress in the understanding of molecular mechanisms preventing an effective antitumor immune response in oral cancer; The latter due to the production of chemical mediators that induce an anti-inflammatory regulatory response that favors tumor development through the vitamin D signaling pathway. The study was published in Frontiers in Immunology on May 7, 2021. Oral cancer, 90% of which corresponds to the squamous cell type, is a neoplasm with a high mortality and morbidity rate, mainly because the diagnosis is made in late stages when metastases already exist, and where treatment produces serious physical and functional sequel among survivors. It is well known that the immune system plays a key role in the development of cancer, either by stimulating pathways that play an anti-tumor role or, conversely, by generating an anti-inflammatory environment that allows the tumor to grow and be spread. The main biological agents of the immune system are lymphocytes or T cells, which have different functions or phenotypes. In cancer, the presence of regulatory T cells (Tregs) and helper T cells type 2 (Th2) are associated with a worse prognosis, whereas the responses of helper T cells type 1 (Th1) within tumors, in general, show a better prognosis. Dr. Nova-Lamperti points out that a key question in oral cancer is how an anti-inflammatory microenvironment is induced, [...]

Using proteogenomics to improve the treatment of squamous cell carcinoma

Source: blogs.bcm.edu, Baylor College of Medicine Author: Molly Chiu Patients with head and neck squamous cell carcinoma (HNSCC), the sixth most common epithelial cancer worldwide, are treated with surgery, chemotherapy and radiotherapy. In addition, targeted agents, including an EGFR monoclonal antibody (mAb) inhibitor and two programmed cell death protein 1 (PD-1) inhibitors, have been approved by the U.S. Food and Drug Administration for HNSCC treatment, but response rates are moderate. In this study, researchers led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated what new insight proteogenomic analysis might offer into understanding why certain patients respond to certain treatments while other patients do not. They propose that their findings may help better match patients to an appropriate course of treatment in the future. Building a proteogenomic profile The team profiled proteins, phosphosites (a site on a protein associated with phosphorylation) and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies. “We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be a good candidate for a different type of therapy – EGFR inhibitors, CDK inhibitors or immunotherapy,” said Dr. Bing Zhang, lead contact of the study and professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor. “We also identified candidate biomarkers that could be used to match patients to effective [...]

2021-02-04T21:09:30-07:00February, 2021|Oral Cancer News|

Oral cancer prognostic signature identified

Source: www.eurekalert.org Author: press release Researchers in Brazil have identified a correlation between oral cancer progression and the abundance of certain proteins present in tumor tissue and saliva. The discovery offers a parameter for predicting progression of the disease - whether cervical lymph node metastasis is present, for example - and points to a strategy for overcoming the limitations of clinical and imaging exams. It could also help guide the choice of an ideal treatment for each patient. The study began in the discovery phase with a proteomic analysis of tissue from different tumor areas using 120 microdissected samples. In the verification phase, prognostic signatures were confirmed in approximately 800 tissue samples by immunohistochemistry and in 120 samples by targeted proteomics. The study was supported by São Paulo Research Foundation - FAPESP and conducted at the National Energy and Materials Research Center (CNPEM) in partnership with the São Paulo State Cancer Institute (ICESP), the University of Campinas's Piracicaba Dental School (FOP-UNICAMP), the Institute of Computing from the same university, the University of São Paulo's Mathematics and Computer Science Institute (ICMC) in São Carlos, and the Dental School of the West Paraná University (UNIOESTE), in addition to other institutions in Brazil and abroad. "The data led to robust results that are highly promising as guides to defining the severity of the disease. We suggested potential markers of the disease in the first phase of the study and verified these markers in the second phase, enhancing the reliability of the findings and [...]

2018-12-06T12:27:03-07:00December, 2018|Oral Cancer News|

Scientists map interactions between head and neck cancer and HPV virus

Source: medicalxpress.com Author: staff, Gladstone Institutes Human papillomavirus (HPV) is widely known to cause nearly all cases of cervical cancer. However, you might not know that HPV also causes 70 percent of oropharyngeal cancer, a subset of head and neck cancers that affect the mouth, tongue, and tonsils. Although vaccines that protect against HPV infection are now available, they are not yet widespread, especially in men, nor do they address the large number of currently infected cancer patients. Patients with head and neck cancer caused by HPV respond very differently to treatments than those whose cancer is associated with the consumption of tobacco products. The first group generally has better outcomes, with almost 80 percent of patients surviving longer than 5 years after diagnosis, compared to only 45-50 percent for patients with tobacco-related cancers. To better understand what might cause these differences, a team of scientists led by Nevan J. Krogan, Ph.D., senior investigator at the Gladstone Institutes, is taking a unique approach by focusing on the cancer-causing virus. They recently mapped the interactions between all HPV proteins and human proteins for the first time. Their findings are published today in the journal Cancer Discovery. "With our study, we identified several new protein interactions that were previously not known to cause cancer, expanding our knowledge of the oncogenic roles of the HPV virus" said Krogan, who is also a professor of cellular and molecular pharmacology at UC San Francisco (UCSF) and the director of the Quantitative Biosciences Institute (QBI) at [...]

2018-09-13T08:58:41-07:00September, 2018|Oral Cancer News|

Wisconsin scientists grow functional vocal cord tissue in the lab

Source: www.med.wisc.edu Author: press release Madison, Wisconsin - University of Wisconsin scientists have succeeded in growing functional vocal-cord tissue in the laboratory, a major step toward restoring a voice to people who have lost their vocal cords to cancer surgery or other injuries. Dr. Nathan Welham, a speech-language pathologist, and colleagues from several disciplines, were able to bioengineer vocal-cord tissue able to transmit sound, they reported in a study published today in the journal Science Translational Medicine. About 20 million Americans suffer from voice impairments, and many have damage to the vocal-cord mucosae, the specialized tissues that vibrate as air moves over them, giving rise to voice. While injections of collagen and other materials can help some in the short term, Welham says not much can be done for people who have had larger areas of their vocal cords damaged or removed. “Voice is a pretty amazing thing, yet we don’t give it much thought until something goes wrong,” says Welham, an associate professor of surgery in the UW School of Medicine and Public Health. “Our vocal cords are made up of special tissue that has to be flexible enough to vibrate, yet strong enough to bang together hundreds of times per second. It’s an exquisite system and a hard thing to replicate.” Welham and colleagues began with vocal-cord tissue from a cadaver and four patients who had their larynxes removed but did not have cancer. They isolated, purified and grew the cells from the mucosa, then applied them to [...]

2015-11-21T09:45:52-07:00November, 2015|Oral Cancer News|

Number of immune cells in tumors could soon help predict and treat cancers

Source: www.science20.com Authors: Emma King, University of Southampton and Christian Ottensmeier, University of Southampton Immune cells in the blood primarily defend us against infection. But we’re now learning that these cells can also keep us free from cancer. Patients with less efficient immune systems such as organ transplant recipients or those with untreated HIV, for example, are more susceptible to cancers. It is also becoming increasingly apparent that we can use immune cells to predict survival in people who do develop cancer. And that, in fact, there are immune cells within cancers. Head and neck cancer underway The number of immune cells inside a tumor can hugely vary: some patients have vast numbers while some have very few. In a recent study, we showed that in head and neck cancers, the survival of a patient depends on how many immune cells are within the tumor. This could be a valuable way of individualizing cancer treatments. Patients with lots of immune cells, for example, could be offered less toxic cancer treatment while those with few immune cells may need more aggressive treatment to improve their chances of survival. Not all immune cells within the tumor are able to “attack” the cancer. By looking at specific cell markers – proteins on the cell exterior that allow us to see whether, for example, cells are exhausted – we can determine which individual immune cells in the tumor will be effective in tackling the cancer, or if they are exhausted and not [...]

2014-09-26T06:21:57-07:00September, 2014|Oral Cancer News|

Study reveals genetic diversity within tumors predicts outcome in head and neck cancer

Source: bionews-tx.com Researchers at the Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear Infirmary have developed a new way to predict the survival rate of patients who have squamous cell carcinoma of the head and neck, thanks to a study partially funded by a CPRIT grant. One of the problems with treating cancer is the degree of genetic heterogeneity within a tumor. What this means is that there are sub populations of tumor cells within a given tumor that have different mutations. This makes the cancer difficult to treat because some cells due to their different mutations will be resistant to the same treatment. According to Edmund Mroz, PhD at the MGH center for Cancer Research (lead author of a report in Cancer on May 20, 2013), this new method of measuring genetic heterogeneity can be applied to a wide range of cancers. (Additional co-authors included Curtis Pickering, PhD, and Jeffrey Myers, MD, PhD, both from the University of Texas M.D. Anderson Cancer Center.) Prior to this study, genes and proteins that are involved with treatment resistance have been identified, however, there has been no way to measure tumor heterogeneity to predict patient survival. Mroz and his group of researchers working in the lab of James Rocco, MD, PhD at MGH developed this new measure by looking at advanced gene sequencing data to calculate a number that indicates the genetic variance found in sub populations of cells within a tumor. They dubbed this new procedure as the mutant-allele tumor [...]

Rating HPV biomarkers in head, neck cancers

Source: www.sciencecodex.com Not all head and neck cancers are created equal. Those started by infection with the human papillomavirus are less often fatal than those with other causes, such as smoking. Detection of a reliable fingerprint for HPV could help patients avoid unnecessarily harsh treatment. A new study finds that while one popular biomarker for HPV is not a reliable predictor of mortality from the cancers alone, combinations of some biomarkers showed much more promise. "Everybody who has studied it has shown that people with virally associated disease do better," said Karl Kelsey, aprofessor of epidemiology and pathology and laboratory medicine at Brown University, and corresponding author of the study in Cancer Research. "There are now clinical trials underway to determine if they should be treated differently. The problem is that you need to appropriately diagnose virally related disease, and our data suggests that people need to take a close look at that." In the study, Kelsey and his multi-institutional team of co-authors measured the ability of a variety of biomarkers to predict mortality from head and neck squamous cell carcinoma (HNSCC). Their data came from hundreds of adult head and neck cancer patients in the Boston area that they have been tracking since late 1999. As part of that data set, they were able to look at blood serology and tumor tissue samples, and they interviewed participants about risk behaviors such as smoking and drinking. DNA alone not reliable One of the most important findings of the study, Kelsey [...]

2012-09-18T13:41:39-07:00September, 2012|Oral Cancer News|

Demystifying the immortality of cancer cells

Source: http://medicalxpress.com/ Author: In cancer cells, normal mechanisms governing the cellular life cycle have gone haywire. Cancer cells continue to divide indefinitely, without ever dying off, thus creating rapidly growing tumors. Swiss scientists have discovered a protein complex involved this deregulated process, and hope to be able to exploit it to stop tumor formation in its tracks. All our cells come equipped with an automatic self-destruct mechanism; they are programmed to die after a certain number of divisions. This internal clock is of great interest to cancer researchers, because most forms of cancer exhibit a defect in this innate timing mechanism. Cancer cells continue to divide indefinitely, long past the moment at which a normal cell would self-destruct. A team of researchers from professor Joachim Lingner’s laboratory at EPFL has learned how this defect is regulated in a tumor. Post-doctoral researcher Liuh-Yow Chen led the team in publishing an article appearing in the journal Nature on the 4th of July 2012. Their hope is that the discovery will provide new targets for drug therapies to combat the deadly disease. Cellular immortality, which is responsible for cancer formation, hearkens back to a critical function of the cells of the developing embryo. At the ends of every chromosome there is a special sequence of DNA known as a telomere, whose length is governed by the telomerase enzyme. This sequence represents the lifespan of the cell. Every time the cell divides, it is shortened, and when the telomere finally runs out, [...]

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