Georgetown Lombardi Comprehensive Cancer Center

Washington, DC, United States

Georgetown Lombardi Comprehensive Cancer Center

Washington, DC, United States
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Receive press releases from The Children's Cancer Foundation, Inc.: By Email The Children’s Cancer Foundation, Inc. (CCF) Highlights Critical Pediatric Cancer Treatment Research at 2nd Annual Research Symposium on June 7, 2017 Columbia, MD, April 16, 2017 --( Each year in the U.S., more than 50,000 children are diagnosed with cancer, and approximately 1000 will die. While the survival rate has improved in the last thirty years, cancer treatment for children is decades behind their adult counterparts. This disparity is primarily a result of the lack of interest from pharmaceutical firms for a variety of reasons including fewer patients and regulatory issues that limit future profits. Most impacted families find this outlook unacceptable, and quickly learn how important it is for the government to provide research funding, specifically to treat and cure pediatric cancer. However, of the current U.S. federal government cancer research budget, managed through the National Institutes of Health, only 4% is allocated for pediatric cancer research. Further, given the recent proposed U.S. budget from the White House, this 4% is widely considered in jeopardy. The Children’s Cancer Foundation, Inc. recognizes the necessity of innovative pediatric cancer research, and, with its Scientific Advisory Board, will hold its 2nd Annual CCF Research Symposium on June 7th. This free, day-long event, entitled “New Drugs for New Cures,” will highlight the latest activity in treatment for cancers such as sarcomas, embryonal tumors, brain cancers, and leukemia. A dozen leading pediatric oncology researchers will discuss the advancements of their work, while others will display poster presentations covering research efforts. The day’s keynote will be Gregory H. Reaman, M.D., Associate Director for Oncology Sciences in the Office of Hematology and Oncology in the Center for Drug Evaluation and Research at the FDA. Dr. Reaman is a leading voice for pediatric cancer research and directed the Center for Cancer and Blood Disorders at the Children’s National Medical Center for more than 17 years. “The CCF and its Scientific Advisory Board hopes that these annual symposia call attention to the remarkable work happening in the field of pediatric oncology, as well as the necessity to fund these efforts in their beginning stages,” offered Jeffrey Toretsky, M.D., Chair of the CCF Scientific Advisory Board, and Researcher at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Toretsky is also a recipient of CCF research funding that began over 20 years ago, when his early work was a collection of ideas in need of financial support to generate data. “CCF’s founder, Shirley Howard, started her work in 1983 and helped transform pediatric oncology facilities into family- and child-supportive environments throughout the Baltimore-D.C. region. While CCF continues to support these facilities and the programs that support current pediatric cancer patients, we recognize the critical need to fund innovative strategies that are unique to pediatric oncology research. Those early dollars can help researchers advance their theories, and ultimately lead to more effective treatment and cures for pediatric cancer,” explains CCF Executive Director Tasha Museles. CCF anticipates more than 200 attendees, largely from the medical research community, but also advocates, families and others seeking a better understanding of the area’s latest pediatric oncology research. For the second year in a row, the symposium will be hosted in Landover at the Giant Food Headquarters, a longtime supporter of CCF. For more information and to register, please visit the CCF website at http://www.childrenscancerfoundation.org or contact the CCF offices at 443-546-4479 and info@childrenscancerfoundation.org. Founded in 1983, The Children’s Cancer Foundation, Inc. is a 501 (c)(3) non-profit organization dedicated to the treatment and cure of childhood cancer in the Maryland, D.C. and Northern Virginia region. CCF has awarded more than $36.6 million dollars to support facilities, research and programs to benefit pediatric cancer patients and their families. Columbia, MD, April 16, 2017 --( PR.com )-- The Children’s Cancer Foundation, Inc. (CCF) highlights critical pediatric cancer treatment research at 2nd Annual Research Symposium on June 7, 2017Each year in the U.S., more than 50,000 children are diagnosed with cancer, and approximately 1000 will die. While the survival rate has improved in the last thirty years, cancer treatment for children is decades behind their adult counterparts. This disparity is primarily a result of the lack of interest from pharmaceutical firms for a variety of reasons including fewer patients and regulatory issues that limit future profits.Most impacted families find this outlook unacceptable, and quickly learn how important it is for the government to provide research funding, specifically to treat and cure pediatric cancer. However, of the current U.S. federal government cancer research budget, managed through the National Institutes of Health, only 4% is allocated for pediatric cancer research. Further, given the recent proposed U.S. budget from the White House, this 4% is widely considered in jeopardy.The Children’s Cancer Foundation, Inc. recognizes the necessity of innovative pediatric cancer research, and, with its Scientific Advisory Board, will hold its 2nd Annual CCF Research Symposium on June 7th. This free, day-long event, entitled “New Drugs for New Cures,” will highlight the latest activity in treatment for cancers such as sarcomas, embryonal tumors, brain cancers, and leukemia. A dozen leading pediatric oncology researchers will discuss the advancements of their work, while others will display poster presentations covering research efforts. The day’s keynote will be Gregory H. Reaman, M.D., Associate Director for Oncology Sciences in the Office of Hematology and Oncology in the Center for Drug Evaluation and Research at the FDA. Dr. Reaman is a leading voice for pediatric cancer research and directed the Center for Cancer and Blood Disorders at the Children’s National Medical Center for more than 17 years.“The CCF and its Scientific Advisory Board hopes that these annual symposia call attention to the remarkable work happening in the field of pediatric oncology, as well as the necessity to fund these efforts in their beginning stages,” offered Jeffrey Toretsky, M.D., Chair of the CCF Scientific Advisory Board, and Researcher at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Toretsky is also a recipient of CCF research funding that began over 20 years ago, when his early work was a collection of ideas in need of financial support to generate data.“CCF’s founder, Shirley Howard, started her work in 1983 and helped transform pediatric oncology facilities into family- and child-supportive environments throughout the Baltimore-D.C. region. While CCF continues to support these facilities and the programs that support current pediatric cancer patients, we recognize the critical need to fund innovative strategies that are unique to pediatric oncology research. Those early dollars can help researchers advance their theories, and ultimately lead to more effective treatment and cures for pediatric cancer,” explains CCF Executive Director Tasha Museles. CCF anticipates more than 200 attendees, largely from the medical research community, but also advocates, families and others seeking a better understanding of the area’s latest pediatric oncology research.For the second year in a row, the symposium will be hosted in Landover at the Giant Food Headquarters, a longtime supporter of CCF. For more information and to register, please visit the CCF website at http://www.childrenscancerfoundation.org or contact the CCF offices at 443-546-4479 and info@childrenscancerfoundation.org.Founded in 1983, The Children’s Cancer Foundation, Inc. is a 501 (c)(3) non-profit organization dedicated to the treatment and cure of childhood cancer in the Maryland, D.C. and Northern Virginia region. CCF has awarded more than $36.6 million dollars to support facilities, research and programs to benefit pediatric cancer patients and their families. Click here to view the list of recent Press Releases from The Children's Cancer Foundation, Inc.


WASHINGTON (May 19, 2017) -- Georgetown University today announces it has exclusively licensed worldwide intellectual property (IP) rights to develop and commercialize uses of tyrosine kinase (TK) inhibitors for the treatment of neurodegenerative diseases to Axovant Sciences GmbH. The application of TK inhibiting compounds for use in neurodegenerative diseases was discovered by a Georgetown University Medical Center (GUMC) researcher. Georgetown holds an issued patent and several pending patent applications for the use of select TK inhibitors for the treatment of certain neurodegenerative diseases. Charbel Moussa, MBBS, PhD, scientific and clinical research director for GUMC's Translational Neurotherapeutics Program, is the named inventor on the IP. "The mechanism by which tyrosine kinase inhibitors affect neurodegenerative disorders appears to involve autophagy in the clearance of neurotoxic proteins associated with neurodegenerative diseases," explains Moussa, an assistant professor in GUMC's Department of Neurology. Moussa collaborated with Fernando Pagan, MD, director of the Movement Disorders Program at MedStar Georgetown University Hospital who is the principal investigator on a phase II, randomized, double-blind, placebo-controlled clinical trial, which launched earlier this year to evaluate the safety and tolerability of low doses of nilotinib, a tyrosine kinase inhibitor, in Parkinson's disease. A second study also was launched for Alzheimer's disease, on which R. Scott Turner, MD, PhD, director of GUMC Memory Disorders Program, is principal investigator. "Our understanding of the autophagy process in neurodegenerative diseases represents the newest frontier of neurotherapeutic research and changes the paradigm on how we think about these diseases," Moussa says. Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).


News Article | May 18, 2017
Site: www.sciencedaily.com

A new investigation of more than 48,000 stored tumor samples finds evidence of a key deficiency in a repair mechanism designed to keep DNA from being mutated and causing cancer. The DNA repair deficiency, called homologous recombination deficiency, or HRD, has previously been studied in only a few cancers, but as researchers at Georgetown Lombardi Comprehensive Cancer Center report, HRD can be found in all of the cancer types the researchers studied, including prostate, breast, cervical, and endometrial cancers as well as two of the more deadly types: ovarian cancer and glioma, a type of brain cancer. The researchers say the findings could play an important role in identifying which mutated genes, and which types of cancer, could be targeted to take advantage of the deficiency and ultimately help in treating the cancer. The abstract describing the work was released today. Additional details will be presented at the American Society of Clinical Oncology annual meeting next month in Chicago. "We know that patients with BRCA mutations are at high risk for developing breast, as well as pancreatic, ovarian, prostate and other cancers, and we have learned over time that BRCA plays a very important role in DNA damage repair. But BRCA is just one of the many genes that encode important proteins in the DNA repair pathway known as homologous recombination," says the study's lead author, Arielle Heeke, MD, a clinical fellow at Georgetown Lombardi Comprehensive Cancer Center. "With ongoing studies of the homologous recombination pathway and its impact on cancer development, we may identify additional genes that, when mutated, allow for either improved response to specific treatments or conversely, portend more aggressive tumor biology, and this could greatly inform development of new cancer therapies," Heeke explains. In this study, Lombardi researchers partnered with Caris Life Sciences, Inc. Caris performed the molecular profiling on 48,733 solid tumor samples to assess the prevalence of homologous recombination deficiency in about 20 different types of solid tumors. The investigators identified evidence of HRD-related mutations in 11.61 percent of them, with the highest concentration of mutations in endometrial cancer, gliomas, and ovarian cancers (38, 15 and 12 percent respectively). The most commonly mutated genes were found to be the ATM, PTEN, BRCA2, BRCA1, and ATRX genes. "We do not yet know the clinical impact of many of these mutations. However, several clinical trials are currently underway to assess a type of therapy that inhibits a DNA repair enzyme known as PARP in tumors with HRD," said Heeke. "In fact, Lombardi has a clinical trial that will open this summer evaluating the use of a PARP inhibitor in patients with tumors with this key deficiency." Heeke says the study would be open to people whose tumors have evidence of HRD like those found in this study, which includes bladder, breast, cervix, liver and bile duct, colorectal, endometrial, gastric/esophageal, head & neck, kidney, neuroendocrine, lung, ovarian, pancreas, prostate, sarcoma, and thyroid cancers, as well as gastrointestinal stromal tumors, glioma, melanoma and unknown primary cancers. The trial "Niraparib Plus Carboplatin in Patients with Homologous Recombination Deficient Advanced Solid Tumor Malignancies" is not yet recruiting patients for enrollment. "If, as we postulate, the combination of chemotherapy and PARP inhibition is successful in treating patients with HRD tumors, I expect that others will start exploring whether similar drugs or analogous therapies can make a difference in these diseases," Heeke concludes.


News Article | May 17, 2017
Site: www.eurekalert.org

WASHINGTON (May 17, 2017) -- A new investigation of more than 48,000 stored tumor samples finds evidence of a key deficiency in a repair mechanism designed to keep DNA from being mutated and causing cancer. The DNA repair deficiency, called homologous recombination deficiency, or HRD, has previously been studied in only a few cancers, but as researchers at Georgetown Lombardi Comprehensive Cancer Center report, HRD can be found in all of the cancer types the researchers studied, including prostate, breast, cervical, and endometrial cancers as well as two of the more deadly types: ovarian cancer and glioma, a type of brain cancer. The researchers say the findings could play an important role in identifying which mutated genes, and which types of cancer, could be targeted to take advantage of the deficiency and ultimately help in treating the cancer. The abstract describing the work was released today. Additional details will be presented at the American Society of Clinical Oncology annual meeting next month in Chicago. "We know that patients with BRCA mutations are at high risk for developing breast, as well as pancreatic, ovarian, prostate and other cancers, and we have learned over time that BRCA plays a very important role in DNA damage repair. But BRCA is just one of the many genes that encode important proteins in the DNA repair pathway known as homologous recombination," says the study's lead author, Arielle Heeke, MD, a clinical fellow at Georgetown Lombardi Comprehensive Cancer Center. "With ongoing studies of the homologous recombination pathway and its impact on cancer development, we may identify additional genes that, when mutated, allow for either improved response to specific treatments or conversely, portend more aggressive tumor biology, and this could greatly inform development of new cancer therapies," Heeke explains. In this study, Lombardi researchers partnered with Caris Life Sciences, Inc. Caris performed the molecular profiling on 48,733 solid tumor samples to assess the prevalence of homologous recombination deficiency in about 20 different types of solid tumors. The investigators identified evidence of HRD-related mutations in 11.61 percent of them, with the highest concentration of mutations in endometrial cancer, gliomas, and ovarian cancers (38, 15 and 12 percent respectively). The most commonly mutated genes were found to be the ATM, PTEN, BRCA2, BRCA1, and ATRX genes. "We do not yet know the clinical impact of many of these mutations. However, several clinical trials are currently underway to assess a type of therapy that inhibits a DNA repair enzyme known as PARP in tumors with HRD," said Heeke. "In fact, Lombardi has a clinical trial that will open this summer evaluating the use of a PARP inhibitor in patients with tumors with this key deficiency." Heeke says the study would be open to people whose tumors have evidence of HRD like those found in this study, which includes bladder, breast, cervix, liver and bile duct, colorectal, endometrial, gastric/esophageal, head & neck, kidney, neuroendocrine, lung, ovarian, pancreas, prostate, sarcoma, and thyroid cancers, as well as gastrointestinal stromal tumors, glioma, melanoma and unknown primary cancers. The trial "Niraparib Plus Carboplatin in Patients with Homologous Recombination Deficient Advanced Solid Tumor Malignancies" is not yet recruiting patients for enrollment. "If, as we postulate, the combination of chemotherapy and PARP inhibition is successful in treating patients with HRD tumors, I expect that others will start exploring whether similar drugs or analogous therapies can make a difference in these diseases," Heeke concludes. Co-authors include Filipa Lynce, Michael Pishvaian, and Claudine Isaacs of Georgetown Lombardi, and Tabari Baker of Caris Life Sciences, Inc. Heeke and the other co-authors report having no personal financial interests related to the study. Caris, under the guidance of Baker, provided the tissue and ran the molecular profiling on solid tumor samples collected from across the United States. Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute as a comprehensive cancer center -- the only cancer center of its kind in the Washington, DC area. A part of Georgetown University Medical Center and MedStar Georgetown University Hospital, Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Connect with Georgetown Lombardi on Facebook(Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer). Georgetown University Medical Center (GUMC is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC onFacebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).


News Article | May 17, 2017
Site: www.eurekalert.org

WASHINGTON (May 17, 2017) -- A team of investigators led by researchers at Georgetown Lombardi Comprehensive Cancer Center has found that the tumor mutation load, or TML, in a patient's cancer biopsy varied by age and the type of cancer, along with several other factors. Researchers say the findings are some of the most comprehensive analyses of TML to date as they include 14 types of solid tumors. Over 8,000 tissue samples were included in the study making this one of the larger collections of tumors examined for TML. The abstract describing the work was released today. Additional details will be presented at the American Society of Clinical Oncology annual meeting next month in Chicago. TML is a measurement of the number of mutations in DNA. Mutated DNA can be subsequently translated to harmful changes in proteins. Mutated proteins often appear foreign to the immune system and can therefore activate a robust immune response that can be boosted by immunotherapeutic agents. "One of our more interesting findings was the fact that mutation load increased with age in many cancers," says the study's principal investigator, Mohamed E. Salem, M.D., assistant professor of medicine at Georgetown Lombardi. "Older age correlated closely with TML in most of the cancers we examined, but in some cancers, such as bladder cancer, there was no correlation by age, which also makes for an important observation in a difficult to treat type of cancer." Looking for high levels of mutations in tumor may seem to be a contrary way of looking for what therapies might be most effective to fight cancer. Because immunotherapies work by taking the brakes off the immune system, and hence allowing immune-fighting cells to go after cancer cells, the more mutations a cancer cell has may make it appear more alien to the immune-fighting cells and therefore, a more focused object of attack. If a cell's TML is high, an immunotherapy could be more effective and hence Salem's interest in quantifying TML. Tumor mutation load also could be used as a marker to determine which types of cancer and which patients, or subsets of patients, could most benefit from immunotherapy. "We found that, as expected, melanoma had the highest TML as we know clinically that this type of cancer responds best to immunotherapy," says Salem, also a member of Georgetown Lombardi's Ruesch Center for the Cure of GI Cancer. "Indeed, the mean TML for melanoma was nearly double that of the next highest mean, non-small cell lung cancer. In addition, we see that high TML often occurs in tumors lacking well-known cancer-related genes, like BRAF or NRAS genes in melanoma and EGFR or ALK genes in non-small cell lung cancer. This suggests that immune checkpoint inhibitors may be particularly effective in patients who are not candidates for common targeted therapies in these types of cancer." "Our next step is to validate and correlate TML levels with outcomes in patients who have received immunotherapy. We'll look to see if patients had high TML levels before they started therapy and then determine if those with the highest levels had the best clinical outcome, which is what we might expect," he says. "If validation studies prove helpful, they could be very useful in designing clinical trials for many types of cancer," Salem concludes. Co-authors include John Marshall, Michael Atkins, Jimmy J. Hwang, Geoffrey Thomas Gibney, Georgetown Lombardi; Joanne Xiu, Zoran Gatalica, and Nianqing Xiao, Caris Life Sciences; Heinz-Josef Lenz, USC Norris Comprehensive Cancer Center; Philip Agop Philip, Karmanos Cancer Center: Antoinette R. Tan and Derek Raghavan, Levine Cancer Institute; Wafik S. El-Deiry, Fox Chase Cancer Center; and Edward S. Kim and Anthony Frank Shields, Wayne State University. The work was supported by the Ruesch Center for the Cure of GI Cancers. CARIS provided analysis of the tumor samples. Salem and the other co-authors report having no personal financial interests related to the study. Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute as a comprehensive cancer center -- the only cancer center of its kind in the Washington, DC area. A part of Georgetown University Medical Center and MedStar Georgetown University Hospital, Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer). Georgetown University Medical Center (GUMC is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC onFacebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).


News Article | May 18, 2017
Site: www.sciencedaily.com

A team of investigators led by researchers at Georgetown Lombardi Comprehensive Cancer Center has found that the tumor mutation load, or TML, in a patient's cancer biopsy varied by age and the type of cancer, along with several other factors. Researchers say the findings are some of the most comprehensive analyses of TML to date as they include 14 types of solid tumors. Over 8,000 tissue samples were included in the study making this one of the larger collections of tumors examined for TML. The abstract describing the work was released today. Additional details will be presented at the American Society of Clinical Oncology annual meeting next month in Chicago. TML is a measurement of the number of mutations in DNA. Mutated DNA can be subsequently translated to harmful changes in proteins. Mutated proteins often appear foreign to the immune system and can therefore activate a robust immune response that can be boosted by immunotherapeutic agents. "One of our more interesting findings was the fact that mutation load increased with age in many cancers," says the study's principal investigator, Mohamed E. Salem, M.D., assistant professor of medicine at Georgetown Lombardi. "Older age correlated closely with TML in most of the cancers we examined, but in some cancers, such as bladder cancer, there was no correlation by age, which also makes for an important observation in a difficult to treat type of cancer." Looking for high levels of mutations in tumor may seem to be a contrary way of looking for what therapies might be most effective to fight cancer. Because immunotherapies work by taking the brakes off the immune system, and hence allowing immune-fighting cells to go after cancer cells, the more mutations a cancer cell has may make it appear more alien to the immune-fighting cells and therefore, a more focused object of attack. If a cell's TML is high, an immunotherapy could be more effective and hence Salem's interest in quantifying TML. Tumor mutation load also could be used as a marker to determine which types of cancer and which patients, or subsets of patients, could most benefit from immunotherapy. "We found that, as expected, melanoma had the highest TML as we know clinically that this type of cancer responds best to immunotherapy," says Salem, also a member of Georgetown Lombardi's Ruesch Center for the Cure of GI Cancer. "Indeed, the mean TML for melanoma was nearly double that of the next highest mean, non-small cell lung cancer. In addition, we see that high TML often occurs in tumors lacking well-known cancer-related genes, like BRAF or NRAS genes in melanoma and EGFR or ALK genes in non-small cell lung cancer. This suggests that immune checkpoint inhibitors may be particularly effective in patients who are not candidates for common targeted therapies in these types of cancer." "Our next step is to validate and correlate TML levels with outcomes in patients who have received immunotherapy. We'll look to see if patients had high TML levels before they started therapy and then determine if those with the highest levels had the best clinical outcome, which is what we might expect," he says. "If validation studies prove helpful, they could be very useful in designing clinical trials for many types of cancer," Salem concludes.


News Article | May 17, 2017
Site: www.eurekalert.org

WASHINGTON (May 17, 2017) -- Younger colon cancer patients appear to have more than three times as many mutations in their tumors as older patients, which could lead to more effective treatment decisions, say researchers at Georgetown Lombardi Comprehensive Cancer Center. In the new study, they found that tumor mutation load, or TML, as well as gene mutations that play an important role in DNA repair, were more predominant in the younger patients. The investigators undertook their analysis at a time when the rate of new colorectal cancers in patients ages 45 or younger is increasing. The abstract describing the work was released today. Additional details will be presented at the American Society of Clinical Oncology annual meeting next month in Chicago. According to Mohamed E. Salem, M.D., assistant professor of medicine at Georgetown Lombardi, and senior investigator for the study, viewing high levels of mutations in tumors as a positive may seem counterintuitive, but it could be important to figuring out what therapies would work best. Importantly, he noted that immunotherapies work by taking the brakes off the immune system; the more mutations a cancer cell has, the more alien it appears to the immune-fighting cells hunting for cells that don't belong. In one part of their study, the researchers looked at a biological mechanism known as mismatch repair, which occurs when a DNA strand is replicated and the wrong base is inserted into a strand being copied. If there are mutations in the genes that direct the mismatch repair, then more tumors can arise. In the other part of the study, the investigators looked at TML, which is a count of mutations in DNA. Tying the two factors together is the essence of their finding as a greater number of mismatch repair gene mutations can contribute to a high TML and high tumor mutation loads were seen in more young than old people in the study. The investigators zeroed in on the biology of distal tumors found in the part of the colon closest to the rectum; distal tumors also include those found in the rectum. Distal tumors are on the rise in younger patients and typically convey better survival odds than proximal tumors, which occur further up the colon. The researchers looked at advanced distal tumors from 229 colorectal cancer patients who were a median age of 40 and compared them with distal tumors from 503 patients who were a median age of 71. Most colorectal cancers appear after age 60. Using advanced gene sequencing techniques, the researchers determined the TML for each tissue sample and catalogued which genes were most frequently mutated in those samples. While the researchers found a wide array of mutated genes, many of which play important roles in various types of cancer, there was no statistically significant difference in the rates of mutation in many cancer-causing genes in younger and older patients. There were, however, a few genes were more frequently mutated in younger patients: HER2, NF1, and the DNA mismatch repair genes MSH6, MSH2, and POLE. They say the DNA mismatch repair mutations may explain the higher TML in younger patients. Significantly, high TML was seen in 8.2 percent of young patients vs. 2.6 percent of older patients - over a three-fold difference. "One of the leading theories for why rates of colorectal cancer are increasing in younger patients relates to lifestyle factors, including diet and exercise," says the study's principal investigator, Benjamin Weinberg, MD, chief hematology/oncology fellow at Georgetown Lombardi. "There is also increasing evidence that bacteria and local inflammation of the colon can drive cancer growth. We can now add tumor mutation load to the list of factors and begin exploring if there is a link between TML and these lifestyle factors." In addition to Weinberg and Salem, other authors of this study include John Marshall of Georgetown Lombardi, and Kelsey Poorman and David Arguello of Caris Life Sciences, Phoenix, Ariz. The work was supported by Georgetown Lombardi's Ruesch Center for the Cure of Gastrointestinal Cancer. Weinberg and Salem report having no personal financial interests related to the study. Marshall serves as a private consultant and chief medical officer for Caris, which performed the genetic analysis of the tumor tissue for this research. Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute as a comprehensive cancer center -- the only cancer center of its kind in the Washington, DC area. A part of Georgetown University Medical Center and MedStar Georgetown University Hospital, Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer). Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).


News Article | June 30, 2017
Site: www.eurekalert.org

WASHINGTON (June 30, 2017) -- Based on a new molecular study of tissues biopsied from various parts of the upper digestive tract, researchers at Georgetown Lombardi Comprehensive Cancer Center have identified significant, if subtle, differences in gene mutations and other factors that could help in developing more tailored treatment options for cancer patients. This finding is notable because as the digestive tract winds its way down from the mouth to the rectum, a continuum of cancers can arise, each of which may be amenable to precision treatment. In this study, the researchers focused primarily on small bowel adenocarcinomas (SBAs) and compared them with parts of the upper digestive tract that precede it and follow it - the gastroesophageal area and right-sided colon cancers, respectively. Each section of the gastrointestinal, or GI, tract plays a role in digestion of food and hence has distinct structural as well as molecular differences. The finding will be presented June 30, 2017, at the European Society for Medical Oncology gastrointestinal meeting in Barcelona, Spain. "Our study was undertaken primarily because SBAs are greatly understudied, as well as increasing in incidence nationwide, and we wanted to determine what may make them unique," says Mohamed E. Salem, MD, assistant professor of medicine at Georgetown Lombardi, and principal investigator for the study. "We really didn't have good data on SBAs so we've been treating the tumors as if they were colon cancers and we really need to start treating them based on their unique properties." The investigators looked at 4,278 tumor samples from a tissue repository of patients with GI tract cancers. The researchers were able to clearly identify 531 SBAs; 2,674 gastroesophageal cancers; and 1,073 ride-sided colon cancers. Using a variety of genetic sequencing techniques, they ascertained how well the genes were expressed, or "turned on" to make proteins. They also calculated what is called the tumor mutational load, or TML, which can be a marker for how responsive a tumor is to immunotherapy - which, paradoxically, could indicate that immunotherapy more effective when a higher TML is found. The researchers found a set of frequently mutated genes in SBAs that could be helpful to clinicians when they are looking to use targeted therapies that work best in cancers with specifics mutations. In this case, KRAS, BRAF, BRCA2 and a few other genes were identified in SBAs. Mutations to these genes can affect the choice of therapy as well as how to better target the mutations. Next, the investigators compared the SBA mutations with mutations in the two other parts of the GI tract and found higher and lower mutation frequencies across a wide array of genes. They were able to discern that SBAs were more like colon than gastric cancers. More importantly, though, they found about a two-fold higher PD-L1 expression level for gastroesophageal cancers compared to right-side colon cancers but did not find such a marked difference between those tumors and SBAs. PD-L1 is often used as a marker to indicate if a cancer might be responsive to immunotherapy, and usually the higher the PD-L1 level, the more responsive a cancer would be to certain immunotherapies. "With this study we now have what I think is one of the biggest datasets on SBAs," says Salem. "Previously, investigators studying the colon found very unique differences between the left and ride sides, and our study therefore took advantage of those findings by exploring the differences between ride-sided colon cancers and SBAs. We now see a continuum of molecular changes that occur as these regions of the digestive tract transition from one area to the other." The next step, says Salem, will be to try to correlate these findings with patient treatment outcomes, initially as a retrospective, or backward looking study, and then hopefully design a forward looking clinical trial to determine which treatments may be best for patients with SBAs. In addition to Salem, other authors of this study include Heinz-Josef Lenz, USC Norris Comprehensive Cancer Center; Anthony Shields and Philip Philip, Karmanos Cancer Center; Joanne Xiu and Tabari Baker, Caris Life Sciences; and Jimmy Hwang and John Marshall, Lombardi Comprehensive Cancer Center, Georgetown University. The work was supported by Georgetown Lombardi's Ruesch Center for the Cure of Gastrointestinal Cancer. Salem reports having no personal financial interests related to the study. Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute as a comprehensive cancer center -- the only cancer center of its kind in the Washington, DC area. A part of Georgetown University Medical Center and MedStar Georgetown University Hospital, Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer). Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).


SAN FRANCISCO -- Georgetown University Medical Center autism specialists working with Latino families in Washington, DC, have developed an effective screening program that identifies Latino infants who may be at risk for autism spectrum disorder (ASD), allowing the opportunity for early intervention. Their unique model is being presented at the International Meeting for Autism Research (IMFAR) in San Francisco May 10-13. The years-long, federally-funded effort took a deep dive into Latino cultural norms in order to develop an ethnically sensitive screening methodology. In the year before their study started, very few toddlers in their target population were screened for autism risk -- less than 10 percent of Latino 18-30 month olds received screening -- and no children were identified to be at risk for ASD. At the end of the study and after incorporating the new screening model, more than 90 percent of the infants were screened during well-child doctor visits. Four percent were identified to be at possible risk and referred for more specific ASD testing. "This rate mirrors the rate of positive screens found in studies of U.S. English-language toddlers," says the study's senior investigator, Bruno Anthony, PhD, deputy director for the Georgetown University Center for Child and Human Development, and professor of pediatrics and psychiatry. "It appears that our approach is effectively picking up children that might benefit from early intervention that can improve outcomes such as cognition, peer interactions, language development and strategies to enhance families coping abilities," explains Anthony. The rate of autism, in general in the U.S., is 1 in 68, says Anthony. More than half of infants referred for further assessment from ASD screening are found not to meet criteria for ASD, he adds. The screening program was tested over 18 months at the Unity Health Care's Upper Cordozo Health Center in Washington, DC, which cares for 7,000 infants (0-3 years old) each year, 70 percent of whom are Latino. One in six of the 93,000 District of Columbia residents rely on Unity Health Care services, which treats community members regardless of their ability to pay. The typical screening tool used in the U.S. to diagnose ASD risk is the M-CHAT (the Modified Checklist for Autism in Toddlers), which is a questionnaire for parents regarding the behavior of their child. Positive answers may lead to further testing. But the M-CHAT, even when translated into Spanish, is not commonly being used with Latino parents, says Anthony. "Our prework for this study found that these parents often do not understand the questions, which can be culturally ambiguous," he says. Anthony and his group adapted the implementation of the M-CHAT for Latino population, to include explanations of some questions and oral administration by "family navigators" who were bilingual, bicultural, and who had "lived experience" of raising children diagnosed with ASD or developmental disorders. Over time, physicians and other health care workers at Upper Cardozo gradually took over the screening process from the family navigators. "We found that Latino parents were often not comfortable talking about their child's possible behavioral issues and developmental delays. We had to work hard to give them the sense that this is appropriate and safe in a medical setting," Anthony says. Information from this study allowed the Georgetown and Upper Cardozo team to articulate 10 key steps in integrating a "Supported Screening" model. Unity Health Care has now used the model to implement screening for developmental delays and mental health, according to Anthony. "We are very excited about this finding because it shows that universal screening for ASDs and developmental delays in primary care can be effective if the program is responsive to community and provider needs that inform outreach, family engagement, training, and clinical procedures," says Anthony. The study was funded by the Maternal and Child Health Bureau of the Health Resources & Services Administration (HRSA), project number R40 MC 20171-01. GGeorgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook, Twitter (@gumedcenter) and Instagram (@gumedcenter).

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