Texas 4000 for Cancer Foundation Impact Update 2007 – 2017
How Your Gift is Making Cancer History® Molecular Markers - $450,000 The modern era of cancer care has rapidly transformed in the last decade, due in large part to our ability to identify cancer and its precursors through a variety of technologies. Research into cancer biomarkers — measurable substances that indicate the presence or ensuing development of cancer — has revolutionized how we perform the most basic functions surrounding cancer care, including screening/detection, diagnosis, prognosis, treatment response and disease monitoring. We now can answer some of the most basic questions that significantly increase our ability to successfully treat patients: How can we expect a patient to react to a particular therapy? Can we predict tumor resistance and metastasis potential? Established in 2005, the Kleberg Center for Molecular Markers has been a prominent vehicle through which MD Anderson has helped answer these questions. It identifies patients likely to benefit from specific therapies and develops biomarkers to detect cancer early, while it is easier to treat. The center’s director, Gordon Mills, M.D., Ph.D., chair of Systems Biology, has navigated the program to regularly engage with clinicians and researchers across the institution to produce more than 8,000 molecular markers that can be used for early cancer detection, with only a drop of blood. Efforts through the Kleberg Center for Molecular Markers have resulted in tumor characterizations of 47 different types of cancer from 16 distinct clinics at MD Anderson. Further efforts by the Kleberg Center have resulted in biomarker testing for gliomas, sarcomas, prostate and other types of cancer becoming standard Gordon Mills, M.D., Ph.D. of care at MD Anderson.
The Kleberg Center is proud to have completed the the Ten Thousand Tumors, Ten Thousand Tests, Ten Thousand Therapies (T9) project. This ambitious program has resulted in the targeted genomic sequencing of more than 15,000 cases of cancer at MD Anderson. Thanks to MD Anderson’s designation as a center of excellence for numerous rare cancer types, the Kleberg Center has catalyzed Texas 4000 for Cancer support by identifying novel biomarkers and therapeutically actionable alterations in rare tumors, a historically underfunded area within cancer care. The Kleberg Center has established a rare tumor sequencing project that has resulted in comprehensive (exome/full length gene) gene and transcriptome sequencing of multiple rare tumor types. We have learned that many rare tumors harbor common mutations that could be treated with established therapies we already know work. With this information, and because of our reputation as one of the premier cancer centers for treating rare cancers, we are able to include rare tumor types in clinical trials. We are proud to be considered one of the leading cancer centers sequencing rare tumors, thanks in large part to Texas 4000 for Cancer.
“We want the patient to ‘teach’ us what is important by looking at the genes that nature targeted for cancer. If we know what genes and their proteins are altered when cancer cells divide and multiply, we can better determine how to treat those proteins to stop cancer growth.” -Dr. Gordon Mills
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Texas 4000 Distinguished Professorship - $300,000 The Texas 4000 Distinguished Professorship was established in 2009 for basic and clinical research towards finding a cure for cancer. Its first holder, Qingyi Wei, M.D., Ph.D., professor of Epidemiology, discovered potential biomarkers for genetic susceptibility to, Qingyi Wei, M.D., Ph.D. and possible predictors of survival in, gastric cancer patients. MD Anderson researchers believe that this marker applies for other cancer types as well. Kim-Anh Do, Ph.D., chair of Biostatistics and the second Texas 4000 Distinguished Professor, performed research that has drastically improved our ability to predict patient survival of kidney cancer, as well as our ability to distinguish malignant tissue from healthy tissue using perfusion computed tomography. We now utilize this imaging technology for cancer detection, prognostication and treatment monitoring for various disease sites, including prostate, colorectal, head and neck, lung and liver. With the foundation’s support, Dr. Do has made extraordinary discoveries by harnessing the world’s largest cataloge of genetic mutations responsible for cancer, The Cancer Genome Atlas. Dr. Do used the lung cancer data set to discover potential Kim-Anh Do, Ph.D. biomarkers that reveal different mechanisms of lung tumorigenesis between light smokers and heavy smokers, a finding that may alter treatment decisions significantly moving forward.
Finally, Dr. Do analyzed early-stage breast cancer using technology called high-dimensional molecular inversion probes (MIPs) with full genome quantifications from tumor cells of patients with breast cancer. Her novel methodology identified genes significantly associated with breast cancer, with an emphasis on more aggressive subtypes, such as triple-negative breast cancer (TNBC), for which there are no known treatment targets nor prognostic factors. This discovery has set the stage for research into powerful diagnostic and treatment biomarkers. Effective April 1, 2017, Dr. Do will hold the Electa C. Taylor Chair for Cancer Research, an accomplishment made possible in large part through support from Texas 4000 for Cancer. This has paved the way for the next Texas 4000 Distinguished Professor, Dimitrios Kontoyiannis, M.D., Dimitrios Kontoyiannis, M.D. professor of Infectious Diseases. His focus is on translational mycology research to improve therapeutic options for fungal infections, which are a major cause of morbidity and mortality in cancer patients, particularly those with hematologic cancers. We look forward to introducing you to Dr. Kontoyiannis and familiarizing you further with his work. The Texas 4000 Distinguished Professorship has helped MD Anderson propel itself amongst the leading cancer centers researching, developing and utilizing biomarkers to significantly improve cancer care for patients. This support also allows distinguished faculty members, postdoctoral fellows and graduate students to travel to seminars and conferences around the world to disseminate their knowledge of molecular markers with other institutions.
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Targeted Therapy - $350,000 Most tumors carry a number of alterations that drive their unique biology. The combination of genetic alterations, along with the resulting biology of the tumor, determine the most appropriate therapeutic response. The Center for Targeted Therapy incorporates molecular and genetic information, demographic data and treatment histories into their analyses to improve its ability to accurately predict patient responses to anti-cancer therapies. The collaboration between the Kleberg Center for Molecular Markers and the Center for Targeted Therapy lets researchers use tissue biomarkers to identify those patients who are likely to respond to a drug treatment and to monitor their responses to the drug. This allows them to design therapies to match patients with the best, most effective, least toxic treatments. Led by director ad interim Varsha Gandhi, Ph.D., who is also chair ad interim of Experimental Therapeutics, the Center for Targeted Therapy comprises 60 investigators from a dozen departments. It amassed a comprehensive database that enables the matching Varsha Gandhi, Ph.D. of a new patient’s cancer as closely as possible with the results of our prior experiences with similar patients in order to select optimal targeted therapy for that new patient. The foundation’s support also allows MD Anderson to take what we’ve learned from our patients’ tumors and make the data available to research programs around the world.
Our collaboration with The Cancer Genome Atlas has helped created a map of the genetic abnormalities that exist in cancer cells. MD Anderson is one of only two groups chosen to characterize patient samples from ongoing National Cancer Institute patient studies. This prestigious recognition of our expertise would not have happened without support like that of Texas 4000 for Cancer. Importantly, we have now extended The Cancer Genome Atlas to include our major efforts in ovarian, endometrial and cervical cancers. The Center for Targeted Therapy also continues to provide key core services that assist all investigators at MD Anderson, including: • an siRNA Screening Service to help identify new targets; • a Translational Chemistry Core Facility offering custom synthesis and development services; • a Sequencing and Non-Coding RNA Program to identify undiscovered genes through stateof-the-art genomic research and technology development; • a Disease-Specific Grant Program to help fund research of underserved cancers; and • a program to support research that uses synthetic chemistry to develop specific compounds. Through the Breast Cancer Moon ShotTM and the Ovarian Cancer Moon ShotTM, we are demonstrating how molecular markers can effectively guide therapy. We are extending a personalized approach to treating breast cancer by acquiring and analyzing serial biomarker-guided treatments to those patients who are not responding to standard neoadjuvant chemotherapy. This gene signature-based approach also will benefit our understanding of the next generation of breast trials through assessment of patients’ responses to targeted therapies.
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The University of Texas MD Anderson Children’s Cancer Hospital - $420,000 The University of Texas MD Anderson Children’s Cancer Hospital has been committed to establishing resources and research programs to better understand and treat pediatric cancer. With support from Texas 4000 for Cancer, a group of the nation’s premier pediatric oncologists have made practicechanging discoveries that have the potential to save and lengthen countless lives. Adolescent and Young Adult Leukemia Adolescents and young adults (AYAs) diagnosed with cancer between the ages and 15 and 39 years have unique medical and psychosocial needs. The types of cancers commonly diagnosed in this age group are different than those in younger children and older adults Anna Franklin, M.D. and the biology of these cancers is distinct as well. Anna Franklin, M.D., helped discover that patients treated on pediatric trials had better outcomes than those treated on adult trials.
Targeting Lung Metastasis in Osteosarcoma Osteosarcoma is the most common primary malignant bone tumor in children. Aerosol delivery of various drugs has been effective in treating asthma and other diseases. Since osteosarcoma metastasizes almost exclusively to the lungs, Eugenie Kleinerman, M.D., professor of Pediatrics, reasoned that Eugenie Kleinerman, M.D. aerosol delivery of chemotherapy would allow the use of lower doses, as the drug would go directly to the lung, achieving the needed concentrations without exposing the rest of the body to the agent. We previously demonstrated that local delivery concentrated the chemotherapy, gemcitabine, in the organ where the metastatic tumors are, and resulted in the regression of lung cancer. Your support also generated the preclinical data providing the basis for a National Institutes of Health grant for a Phase I clinical trial of aerosol gemcitabine for the treatment of patients older than 12 and younger than 50 with lung metastases.
Texas 4000 riders present MD Anderson with a check in June of 2015.
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The University of Texas MD Anderson Children’s Cancer Hospital, Cont’d Pediatric Clinical and Translational Research Center A well known and proven clinical model is the use of Asparaginase for the treatment of leukemia cells. Cesar Nunez, M.D., associate professor of Pediatrics, is analyzing a compound that, similar to Asparaginase, has been associated with leukemia and lymphoma regression Cesar Nunez, M.D. among other tumors. An analysis of samples will let us know if this compound may have prospective therapeutic implications similar to what Asparaginase represents at the moment. If that is the case, this model will have the potential to be part of individualized cancer treatment. Universal Biomarker for Sarcoma Detection Shulin Li, Ph.D., has discovered that the protein vimentin is present inside of tumor cells on the surface of freshly isolated metastatic tumor cells obtained from surgically removed metastatic tumors. Based on this discovery of cell surface vimentin (CSV), his lab developed a Shulin Li, Ph.D. circulating tumor cell (CTC) detection technology that can indicate the presence or absence of CTCs in human blood samples across myriad tumor types. MD Anderson has filed a patent application for this first CTC detection tool that extends across tumor types. The goal is to use CTC detection technology to determine when to administer treatment intervention and when to pause or stop treatment. We are also testing this CTC detection system in a clinical trial in
pediatric sarcoma. Because of the rapid progress we have made with CTC detection and quantification, Abnova, Inc. has licensed this technology from MD Anderson. We hope that CTC analysis will provide a broad benefit to patients and that the research community will find new applications for this approach in other cancers. To that end, Dr. Li’s lab has initiated analysis of the CTC subpopulations isolated by CSVbased capture to determine which types of CTCs will be more predictive of survival or of metastasis. At this point, we are comfortable concluding that PD-L1– positive CTCs are more resistant to treatment and are associated with poor survival. Targeting Brain Tumors with NK Cell Therapy David Sandberg, M.D., professor of Neurosurgery, is investigating new methods of treating pediatric brain tumors that have proved resistant to therapy. Dr. Sandberg’s trial is aimed at relapsed and refractory medulloblastoma, ependymoma, and atypical teratoid rhabdoid tumors David Sandberg, M.D. (ATRT) — all of which reside in the fourth ventricle region of the brain, near the base of the skull. This is a more common site for pediatric than adult brain tumors. Since radiation and systemic chemotherapy have been associated with significant side effects in children, this novel method of treatment represents a promising alternative. It might decrease side effects while effectively treating the tumor where it hides. Inserting a catheter into the fourth ventricle at the time of the tumor resection would also avoid an additional operation. Texas 4000 for Cancer seed funding supported this trial, which has successfully provided the exciting proof of principle that intraventricular chemotherapy may be effective in treating malignant brain tumors without causing significant toxicity in the Phase I portion of the trial.
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The University of Texas MD Anderson Children’s Cancer Hospital, Cont’d Additionally, funds from Texas 4000 for Cancer have been used to buy critical equipment, such as a new freezer that maintains samples at appropriate temperatures, as well as a new centrifuge. Prior to this purchase, MD Anderson Children’s Cancer Hospital was relying on loaned equipment to maintain and progress our research projects. Equipment provided by Texas 4000 for Cancer is absolutely essential to the work we do on behalf of pediatric patients. Texas 4000 for Cancer has bolstered MD Anderson across the entire cancer care continuum. We are honored to have the support of your foundation and look forward to our continued partnership. On behalf of all of the programs that benefit from the generosity of Texas 4000 for Cancer, thank you for all that you do for our patients.
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