Research & Grants

Hyundai GRANT RECIPIENTS

Since 1998, Hyundai Hope On Wheels has been awarding innovative research projects at COG institutions across the country. Our grant-winning doctors and researchers are at the frontline of this very important battle. Meet our 2014 grant winners below. You can also review information about previous winners by year.

Dr. James F. Amatruda Dr. James F. Amatruda - Children's Medical Center Dallas

Rhabdomyosarcoma (RMS) is a cancer of muscle and soft tissue in children. RMS is treated with combinations of surgery, chemotherapy and radiation. While the overall cure rates for RMS have improved to more than 70%, children with advanced stage or metastatic disease are much less likely to be cured. In fact, RMS has among the lowest cure rates among childhood cancers. Several decades of attempts to intensify chemotherapy for RMS have not improved these poor outcomes. Recently, however, studies ...

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Dr. Michael Armstrong - Duke University School of Medicine

Neuroblastoma is the third most common cancer affecting children. Over the past two decades, many advances have been made in improving treatment of many childhood cancers. Unfortunately, children with advanced-stage neuroblastoma continue to do poorly, with approximately two-thirds succumbing to their disease, despite very intense treatments. Often, children will go into remission only to have their neuroblastoma tumors return, resistant to all currently available treatments. To improve the outcome of children with neuroblastoma, new therapies need to be developed. The best way to accomplish this is through a ...

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Dr. Elizabeth A. Beierle Dr. Elizabeth A. Beierle - University of Alabama at Birmingham Division of Pediatric Hematology-Oncology

Neuroblastoma, the most common extracranial solid tumor of childhood, remains responsible for over 15% of pediatric cancer deaths. Children with advanced or relapsed disease have dismal outcomes, and it is obvious that novel and innovative therapies will be necessary to successfully combat this devastating tumor. Current therapy for high risk neuroblastoma incorporates retinoic acid (RA), a vitamin A derivative. RA causes cell differentiation and is utilized with the idea that it will direct ...

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Dr. Miriam Bornhorst Dr. Miriam Bornhorst - Children’s National Medical Center

Optic pathway gliomas (OPGs) are the most common tumor in the visual pathway of children. OPGs, while benign, can lead to significant vision loss, impacting patients both medically and psychologically. Up to 70% of OPGs are diagnosed in children affected by Neurofibromatosis 1 (NF1), a common genetically inherited disorder that predisposes children to tumor development through increased activity of the Ras/ERK pathway, a pathway that is important for cell growth. The Ras/ERK pathway can be ...

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Dr. Erin Breese Dr. Erin Breese - Lucile Packard Children’s Hospital

One of the challenging questions in cancer biology is how a normal cell transforms into a cancer cell. Many pediatric cancers are characterized by distinct chromosomal translocations that occur as a result of an error in the repair process following DNA damage. In the majority of infants who develop acute lymphoblastic leukemia (ALL), the leukemia cells are characterized by a chromosomal translocation involving the Mixed Lineage Leukemia (MLL) gene. Infants with MLL-rearranged leukemia have a ...

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Dr. Bill H. Chang Dr. Bill H. Chang - Doernbecher Children’s Hospital Foundation

Acute Lymphoblastic Leukemia (ALL) is one of the more common causes for disease-related mortality in children and adolescents. As we have made great strides in curing ALL we have increased the disparity between the outcomes of children compared to adolescents and young adults (AYA). Therefore, a better understanding of AYA-ALL to develop novel targeted therapies has become essential in hopes to advance the treatment of these diseases. Recent studies from our lab have shown that many patient ...

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Dr. Michael Cleary Dr. Michael Cleary - Lucile Packard Children’s Hospital

Despite significant improvements in the treatment of acute lymphoblastic leukemia (ALL) in past decades, there is still a need to develop more effective and less toxic therapies. Since pediatric ALL represents a heterogeneous collection of orphan diseases with diverse genetic origins, it is increasingly apparent that treatments must be customized for the individual molecular features of each patient’s disease. This application focuses on the pathogenic mechanisms in a distinctive genetic ...

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Dr. Ian J. Davis Dr. Ian J. Davis - UNC Lineberger

Biologically targeted agents have the possibility to change the way that we treat pediatric cancers. The discovery of new classes of medications is needed to make this a reality. Focusing on a class of molecules that act on the way that DNA and its associated proteins interact to turn genes on and off, we have discovered a novel compound with biological activity against Ewing sarcoma. However, much more work needs to be done to figure out why. We will:

• Explore the proteins and pathways that ...

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Dr. Todd E. Druley - St. Louis Children's Hospital

Dr. Druley is a board-certified pediatrician and faculty member in Pediatric Hematology and Oncology at St. Louis Children's Hospital. He is a general oncologist who also participates in the care of bone marrow transplant recipients. His research is based in the hypothesis that much of pediatric cancer predilection and treatment is heavily influenced by the unique combination of rare inherited DNA polymorphisms within each person.

Dr. Druley's research is conducted in Washington University's Center for Genome Sciences, which is composed of a multidisciplinary group of investigators focused on utilizing the ...

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Dr. Muller Fabbri Dr. Muller Fabbri - Children's Hospital Los Angeles

Drug resistance is the main cause of insuccess in the treatment of all types of cancer. The mechanisms of resistance are only poorly understood. Therefore, a better comprehension of such mechanisms could provide us with more effective anti-cancer treatments. I have pioneered the discovery that microRNAs (miRNAs), small RNA molecules secreted by cancer cells in little vesicles called exosomes, can bind to a receptor called Toll-like receptor 8 (TLR8) in surrounding cells of the immune system ...

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Dr. Alan D. Friedman Dr. Alan D. Friedman - Johns Hopkins University

Glioblastoma multiforme (GBM) is a highly aggressive pediatric brain tumor that is uniformly fatal despite aggressive chemotherapy and radiation therapy. The malignant cells in these tumors secrete hormones that attract normal macrophages, a type of white blood cell. Tumor-associated macrophages (TAMs) provide the malignant GBM cells with factors that contribute to their aggressiveness. This research proposal seeks to develop means to alter TAMs so that they now fight the malignant GBM cells ...

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Dr. Charles Gawad Dr. Charles Gawad - St. Jude Children's Research Hospital Memphis

Cancer sequencing studies are cataloguing the genetic alterations that are acquired when normal hematopoietic precursors transform into leukemia, but most mutations are not shared across patients, which limits their use as prognostic markers. Persistent minimal residual disease (MRD) is currently the best predictor of poor patient outcome. However, existing MRD monitoring strategies have suboptimal sensitivity, as most patients that relapse do not have detectable disease during treatment. In ...

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Dr. Kelly C. Goldsmith Dr. Kelly C. Goldsmith - Aflac Center of Children’s Healthcare Atlanta

We will use a unique phospho-protein microarray to investigate changes in activated tyrosine kinases between pre-treatment NB cell lines and their relapsed cell line pair (KCN, KCN-R, pretreatment and Relapsed, respectively, 5 such pairs) and assess if those changes affected Bax expression. We will also use a tyrosine kinase RNA inhibition (RNAi) library to perform a functional synthetic lethal screen to identify kinase pathways affecting Bax activity in NB.

 

Dr. Peter Gordon Dr. Peter Gordon - University of Minnesota Medical Center - Fairview

There are ~3000 children and adolescents diagnosed with acute lymphoblastic leukemia (ALL) each year in the United States. This makes ALL the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses. Although the therapy for leukemia has vastly improved, it is still a fatal disease for many children and there remains an urgent need for novel, efficacious, and less toxic therapies. While leukemia begins in the bone marrow, it spreads to other organs such as ...

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Dr. James Anthony Graves Dr. James Anthony Graves - Children's Hospital of Pittsburgh of UPMC

Neuroblastoma is the most common extracranial pediatric tumor. One particular subtype of this disease – tumors with N-Myc
amplification – remains one of the most difficult cancers to cure. We intend to identify new molecular targets for this
disease, given that the current treatment regimens are not only unacceptably ineffective, but highly toxic as well. We have
chosen to focus on mitochondrial biology, as that organelle is the epicenter of many of the so-called “hallmarks of
cancer”1, ...

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Dr. Alex Y. Huang Dr. Alex Y. Huang - Rainbow Babies and Children’s Hospital

Osteosarcoma (OS) is the most common aggressive primary bone cancer in the pediatric and adolescent population. Half of all new cases of OS diagnosed in the U.S. occur in children and young adults, and about 20% of these patients have metastatic spread, while others developed lung metastasis after initiation of therapy. Lung metastasis in OS responds poorly to conventional chemotherapy, which accounts for most of the mortality. Recent exciting scientific development implicates the immune system ...

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Dr. Catriona Jamieson Dr. Catriona Jamieson - Rady Children’s Hospital

Leukemia is the commonest childhood cancer. Newer therapies are required to minimize
chemotherapy related morbidity and risk of relapse, which are significant problems. The
commonest form of childhood leukemia is associated with an abnormal gene, TELAML1,
which arises in the developing baby during pregnancy and generates a preleukemic
population of abnormal cells. The abnormal cells are clinically silent and do not
cause any symptoms. When these pre-leukemic cells acquire further ...

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Dr. Emmanuel Katsanis Dr. Emmanuel Katsanis - University of Arizona

Advances in haploidentical bone marrow transplantation (h-BMT) have increased the treatment options for patients without a match, as half match parents or siblings can now be used safely as donors. The possibility of significantly reducing the complications of graft versus host disease with the administration of post-transplant cyclophosphamide (PT-CY), has revolutionized the applicability of h-BMT. However, disease recurrence remains one of the major challenges in h-BMT with PT-CY. Our ...

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Dr. Gary Kupfer Dr. Gary Kupfer - Yale School of Medicine Department of Pediatrics

Fanconi anemia (FA) is a pediatric genetic disease of cancer susceptibility. Mutations and disordered expression in FA genes have similarly been found in many cancers of non-FA patients, many pediatric, suggesting an avenue for therapeutic intervention based on FA biology may be possible. This strategy is the basis of PARP inhibition in BRCA2 mutant tumors, but investigation in other more common FA genes has been unexplored. Treatment of FA children with malignancies is also extremely ...

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Dr. Alisa B. Lee Sherick Dr. Alisa B. Lee Sherick - Children’s Hospital of Colorado Foundation

Pediatric acute myeloid leukemia (AML) continues to be exceedingly difficult to treat successfully, and requires the use of extremely toxic therapy that often results in long-lasting side effects in children. The unacceptably low overall survival rates and toxicities of current treatments mandate that we find new therapies that will allow us to improve outcomes and quality of life.

Our lab has developed novel drugs that target a protein called the Mer tyrosine kinase, which is present on ...

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Dr. Kasey Leger Dr. Kasey Leger - Seattle Children's Hospital

The battle against pediatric cancer is one of the greatest success stories in medicine. Once considered uniformly fatal, now nearly 80% of children diagnosed with cancer will become long-term survivors. Despite these remarkable strides, the cost of cure is high. Seventy percent of childhood cancer survivors have at least one chronic medical condition attributable to their initial cancer or its therapy. Heart disease is one of the most common causes of treatment-related death in childhood cancer ...

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Dr. Rajen Mody Dr. Rajen Mody - University of Michigan C.S. Mott Children's Hospital

Survival of pediatric cancer patients have improved considerably over the last four decades, however, the survival for patients who present with metastasis or relapse after upfront treatment have remained poor. New insights are urgently needed, especially as to why tumors develop metastasis, resistance to treatment and why patients with same diagnosis respond differently to similar treatment. To answer some of these most challenging questions, National Institute of Health (NIH) leadership and ...

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Dr. Satiro Nakamura De Oliveira Dr. Satiro Nakamura De Oliveira - UCLA Jonsson Comprehensive Cancer Center (Mattel Childrens Hospital)

Non-Hodgkin lymphoma (NHL) is the fifth most common pediatric cancer, accounting for approximately 800 new cases/year. Relapsed or refractory cases have less than 50% of chance of cure. New strategies are required to decrease morbidity and mortality for these patients.
This proposal will evaluate the modification of hematopoietic stem cells (HSC) with an optimized construct of anti-CD19 chimeric antigen receptor (CAR). A novel vector will be used to deliver a CD19-specific, hinge-optimized, ...

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Dr. Tobias Neff Dr. Tobias Neff - Children’s Hospital of Colorado Foundation

My laboratory studies Acute Myeloid Leukemia (AML). Cure rates for pediatric AML cases are unacceptably low. In many patients with high risk AML, even the most aggressive therapies including allogeneic stem cell transplantation cannot control the disease in the long term. There is therefore a need for more effective and less toxic drugs in the treatment of AML.

I am especially interested in epigenetic gene regulation in AML. The field of Epigenetics studies how the genetic material of a ...

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Dr. Allison F. O'Neill Dr. Allison F. O'Neill - Dana Farber Cancer Institute

Ewing sarcoma is a solid tumor, arising from bone and the soft tissues, that affects approximately 250 children, adolescents, and young adults each year. Disease confined to a single site, and successfully treated with chemotherapy and either surgery or radiotherapy, has a favorable prognosis with a 75% likelihood of overall survival. Metastatic disease, conversely, confers a poor prognosis with a less than 20% overall survival. The ability to accurately diagnose disease extent is therefore ...

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Dr. Stuart H. Orkin Dr. Stuart H. Orkin - Dana Farber Cancer Institute

Chronic myelogenous leukemia (CML) is blood cancer caused by mis-arrangement of two chromosomes (a translocation) that generates a fusion cancer gene known as BCR-ABL. The ABL protein has enzyme activity (a kinase) that is inhibited by targeted drugs, such as Gleevec. Indeed, clinical trials demonstrated that treatment with Gleevec converts CML from a fatal blood malignancy (without bone marrow transplantation) to a chronic condition. However, cure of CML is only infrequently achieved because ...

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Dr. Mario Otto Dr. Mario Otto - University of Wisconsin - American Family Children's Hospital

Radiation therapy is a critical component of successful multimodality therapy for most pediatric solid cancers. However, in the setting of disseminated disease the utility of external beam radiotherapy is understandably often limited. Systemically administered, targeted radionuclide therapy may help overcome this challenging situation but unfortunately for most pediatric cancers those do not exist. CLR1404 is a novel small molecule drug that broadly targets malignant cells due to the specific ...

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Dr. Rachel Rau Dr. Rachel Rau - Texas Children's Hospital

Acute lymphoblastic leukemia (ALL) is an aggressive cancer of the blood. ALL is the
most common cancer in children, and despite our best therapy, up to 20% of
children with ALL will not be cured. Therefore, it is important to identify which
patients are at risk for a poor outcome, and to find ways to better treat these
patients. Research has recently identified abnormalities of a gene called IKZF1 in
20-30% of pediatric ALL patients. Patients with IKZF1 abnormalities have a
particularly ...

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Dr. Anish Ray Dr. Anish Ray - Cook Children's Medical Center

Ewing sarcoma family of tumors (ESFT) is the second most common bone and soft tissue cancers diagnosed in children and young adults. Even with intensive therapeutic options, the survival rate in metastatic patients is less than 30%. Hence, novel therapeutic approaches involving strategies to achieve higher efficacy with less toxicity are urgently needed. EWS-FLI1 is a transcription factor and fusion protein which is dysregulated in approximately 80% of ESF tumors. Survivin is an inhibitor of ...

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Dr. Miguel Rivera Dr. Miguel Rivera - Massachusetts General Hospital

Wilms tumor is the most common pediatric kidney cancer and is treated with a combination of surgery, chemotherapy and radiation therapy. Despite improvements in treatment, 10-15% of cases do not respond to current therapies. There is thus a pressing need to identify targeted therapies that will decrease toxicity and improve survival. Wilms tumors are thought to originate from kidney stem cells and to be closely related to kidney development. The mechanisms that regulate these stem cells and ...

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Dr. Brian R. Rood Dr. Brian R. Rood - Children’s National Medical Center

The most prevalent theory of cancer formation contends that cancer is largely initiated by random genetic events (mutations) and that “bad luck” largely determines who gets cancer. We plan to challenge this dogma by answering two questions: First, what are the features of a cellular environment that permit or even potentiate cancerous transformation? Second, are these features constitutionally present in the genetics of the host before tumorigenesis and therefore can cancer formation in an ...

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Dr. Lisa Roth Dr. Lisa Roth - Weill Medical College of Cornell University

Burkitt lymphoma is a highly aggressive cancer that occurs primarily in children. Although significant advances have been in treatment, therapy requires high dose, intensive chemotherapy which can have significant short and long term effects. For patients with relapsed disease, there are few treatment options and the majority of children will die of their disease. Targeted cancer therapy where only cancerous cells are killed and healthy cells are spared would be of great benefit. This type of ...

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Dr. Noriko Satake Dr. Noriko Satake - UC Davis Cancer Center

B-cell type acute lymphoblastic leukemia (ALL) is the most common cancer in children. Up to 25% of children with ALL have poor outcomes with only 30% survival rate. Also, current ALL treatments are highly toxic to growing children, resulting in both short- and long-term irreversible side effects. To overcome these challenges, we have developed a novel targeted therapy using an antisense oligonucleotide (ASO) directly conjugated to a monoclonal antibody with promising results. The goal of ...

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Dr. Prakash Satwani Dr. Prakash Satwani - Columbia University Medical Center

Although outcomes for children with newly diagnosed acute leukemia have improved significantly, patients who have refractory or relapsed disease continue to have dismal prognoses. Therefore, there remains an unmet need for novel therapies to salvage patients with refractory/relapsed acute leukemia.

Natural killer (NK) cells are immune cells that have the ability to recognize and eliminate cancer cells. NK cells bind to proteins called “NK cell ligands” which are expressed on cancer cells. ...

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Dr. Mary Lou Schmidt Dr. Mary Lou Schmidt - Children's Hospital of Philadelphia

The Hyundai Hope of Wheels Clinical Program Award will be used to expand the reach of COG research and engage all babies, children, adolescents and young adults with cancer treated at the University of Illinois, Rush University and Stroger (formerly Cook County Hospital) Medical Centers. We seek to engage all clinicians from every department caring for this broad population including Pediatric and Medical Oncology, Orthopedics, Ophthalmology, and Neurology/Neurosurgery to offer patients access ...

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Dr. Alix Seif Dr. Alix Seif - Children's Hospital of Philadelphia

T cells are immune cells that identify and kill infected or cancerous cells, while “tolerating” (not attacking) healthy cells. Acute lymphoblastic leukemia (ALL) is a blood cancer that "tricks” T cells into tolerating it. Researchers have developed ways to help T cells target a specific feature on ALL called an “antigen”. These treatments allow T cells to recognize and kill ALL very effectively. However, in some children, the ALL comes back after losing the antigen being targeted. In other ...

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Dr. Barbara Spitzer Dr. Barbara Spitzer - Memorial Sloan-Kettering Cancer Center

Leukemia is a cancer of the blood cells, and it is the most common form of childhood cancer. Acute myeloid leukemia (AML), in particular, has a fairly low survival rate, with five-year survivals of less than 40%. There are some subtypes of AML with particularly poor outcomes, with survival rates falling below 20%. Patients with these types of AML may benefit from new agents and targeted therapies to improve their chances of long-term survival. One of these groups of patients, those with AML ...

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Dr. Katherine Tarlock Dr. Katherine Tarlock - Fred Hutchinson Cancer Research Center

The mutation FLT3/ITD is common in acute myeloid leukemia (AML) and causes inappropriate growth and survival of leukemia cells. Children with FLT3/ITD have a poor prognosis with chemotherapy alone and new therapies are urgently needed. The role of targeted therapy inhibiting FLT3 to achieve leukemia cell death is currently being evaluated, and despite an initial response, many patients experience disease progression as the leukemia develops new strategies to survive and resist the chemotherapy. ...

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Dr. Jeffrey W. Taub Dr. Jeffrey W. Taub - Children's Hospital of Michigan

In contrast to the tremendous success in the treatment of pediatric acute lymphoblastic leukemia over the last three decades, improvements in acute myeloid leukemia (AML) therapy have been modest, as 20-40% of patients do not respond to initial chemotherapy, and approximately 50% of responding patients will eventually relapse. Patients who relapse are more resistant to chemotherapy and patient outcomes are very poor. Therefore, new therapies for children with AML need to be developed including ...

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Dr. Jeffrey A. Toretsky Dr. Jeffrey A. Toretsky - Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Metastatic Ewing sarcoma (ES) typifies a cancer with potent circulating tumor cells (CTC); current therapies effectively eliminate the bulk of the tumor, however, metastatic recurrence is common. The etiology of relapse after radiographic complete remission remains unknown. CTC that leave a primary tumor, enter the circulation, and establish metastases at distant sites may be cancer stem cells (CSC), but this is not proven. Our published papers demonstrated that aldehyde dehydrogenase (ALDH) ...

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Dr. Michael Verneris Dr. Michael Verneris - University of Minnesota Medical Center - Fairview

Children with high risk or relapsed sarcomas have little if any possibility for curative therapy. To grow, sarcomas rely upon external growth factors, including epidermal growth factor (EGF). Here we describe two new approaches to devise treatments for children (and adults) with high risk sarcoma. In the first approach, we have made two different compounds (“drugs”) that consist of the EGF growth factor connected to a cell toxin. As the growth factor binds to the cancer cell, it is ...

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Dr. Jiwang Zhang Dr. Jiwang Zhang - Loyola University Stritch School of Medicine

Although intensive chemotherapy can induce complete remission in most patients, a cure for pediatric acute T-lymphoblastic leukemia (T-ALL) is challenged by disease relapse and drug-resistance. Mutations in the PTEN gene, which commonly correlate to drug-resistance and poor prognosis, have been detected in 15-40% of T-ALL patients. The goal of this study is to develop novel targeted therapies for PTEN-null T-ALL that are less toxic. The conclusions of this study should also benefit children ...

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Dr. Patrick Zweidler-McKay Dr. Patrick Zweidler-McKay - MD Anderson Cancer Center

The goal of this proposal is to develop a new class of therapeutics which activate Notch signaling, e.g. Notch agonists. We and others have found that Notch activation has anti-cancer effects in a subset of cancers, including acute myeloblastic leukemia (AML), B-ALL, neuroblastoma, etc. In this proposal we will test the efficacy of multiple Notch activating approaches which may enhance the efficacy of current therapies for human AML. These agents may also have immune stimulating effects which ...

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