2023 Awardees
UCI Anti-Cancer Challenge
October 05, 2024
October 05, 2024
The UCI Anti-Cancer Challenge is proud to announce the funding of a diverse range of innovative cancer research projects at the UCI Health Chao Family Comprehensive Cancer Center and its pediatric cancer affiliate, Children’s Hospital of Orange County (CHOC).
Through the unwavering support of dedicated participants, donors and supporters who collectively raised more than $1 million in 2023, the UCI Anti-Cancer Challenge has awarded grants to 23 pilot projects and early phase clinical trials, reaching a remarkable milestone of 123 funded projects since 2017. These projects are poised to revolutionize the future of cancer diagnosis, treatment and cures.
By registering for the 2024 UCI Anti-Cancer Challenge, you can help fund the next round of innovative cancer research projects.
TRACK 1: PILOT PROJECTS
Establishment of a Model System to Elucidate Mechanisms of Response and Resistance to Engineered T-cell Therapy in Lymphoma
Investigator
Brian Sworder, MD, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Immune based treatment strategies are increasingly employed to treat patients with non-Hodgkin lymphoma (NHL), but many patients still experience relapse. In this study we seek to develop of method through which we can better understand how mutations in particular genes contribute to treatment resistance following a particular type of immune based therapy called chimeric antigen receptor (CAR) T-cells. If successful, this project will build a foundation for future clinical trials by informing the development of improved immunotherapies for this illness and improve outcomes for patients.
Investigation of Microprotein Contributions to Pancreatic Ductal Adenocarcinoma
Investigator
Thomas Martinez, PhD, Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy & Pharmaceutical Sciences
The identification and characterization of all proteins encoded in the human genome is critical for understanding both normal physiology and disease. Here we will investigate how a class of previously overlooked small proteins impact tumor growth in pancreatic ductal adenocarcinoma. By uncovering novel regulators of tumor growth, we hope to enable the discovery of targeted therapeutics and biomarkers for early diagnosis of this incredibly lethal disease.
Targeting Neoplastic Cell Fate Transitions Through Adhesome Signaling
Investigator
Timothy Downing, PhD, Department of Microbiology & Molecular Genetics, UC Irvine School of Medicine
Our research aims to develop a groundbreaking platform technology that can reveal how cancer cells change over time and in response to treatment. By studying these changes, we hope to identify new ways to treat cancer more effectively and prevent relapse. This innovative approach could lead to personalized treatment options and ultimately improve outcomes and overcome health disparities for cancer patients in our community and around the world.
Exploring Lipid Metabolism in NAFLD-HCC Transition Using Stem Cell Derived Hepatocytes
Investigator
Quinton Smith, PhD, Department of Chemical and Biomolecular Engineering, UC Irvine Samueli School of Engineering
Our research investigates how changes in fat processing within liver cells contribute to the development of liver cancer. We aim to understand how exposure to certain fats, similar to those associated with a common liver disease called NAFLD, affects the behavior of liver cells derived from stem cells. By studying this, we hope to uncover the underlying mechanisms that drive liver cancer development from metabolic dysfunction. Additionally, we will use advanced genetic techniques to introduce specific genetic changes associated with a higher risk of liver disease found in Hispanic populations, to shed light on how genetic factors influencing likelihood of cancer development.
Innovative Approaches to Address Chemoresistance in Prostate Cancer: Integrating Electrokinetic and Microfluidic Technologies
Investigator
Tayloria Adams, PhD, Department of Chemical and Biomolecular Engineering, UC Irvine Samueli School of Engineering
Our research project aims to develop innovative methods to combat chemoresistance in prostate cancer, a disease that disproportionately affects African American men, who experience higher rates of incidence and mortality. By utilizing advanced engineering techniques to study the physical properties of cancer cells and their response to treatment, we seek to understand the underlying mechanisms of chemoresistance. This research is crucial for addressing health disparities and enhancing our understanding of prostate cancer biology, leading to the development of targeted therapeutic interventions. Ultimately, our findings could lead to improved treatment strategies for all individuals affected by prostate cancer, particularly those from marginalized communities, potentially extending and enhancing their quality of life.
Financial Implications of a Pediatric/Adolescent/Young Adult (AYA) Cancer Diagnosis on a Patient’s Quality of Life and Health Outcomes
Investigator
Sonia Morales, MD, MPH, Department of Pediatrics, UC Irvine School of Medicine
Pediatric and adolescent/young adult (AYA) cancer survivors, along with their families, often face financial hardships. To evaluate the health outcomes and financial implications on pediatric/AYA patients with cancer and their parents, longitudinal data is needed, particularly in a culturally diverse population. This study seeks to investigate and characterize how financial hardship correlates to decreased care nonadherence, increased psychological distress and educational/vocational status among pediatric/AYA cancer patients.
HMGB2 Regulation of Anti-Tumor T cell Immunity
Investigator
Roberto Tinoco, PhD, Department of Molecular Biology and Biochemistry, UC Irvine School of Biological Sciences
Few cancer patients respond to current immunotherapies, highlighting the pressing need to identify, develop, and improve treatments that are efficient and safe for patients that presently have no treatment options. The proposed studies will determine whether a new protein in T cells is essential for their ability to kill cancer cells. If successful, the study may lead to new drugs that may improve therapies for cancer patients.
A Novel Gut-Liver Axis as a Risk Factor for Liver Cancer
Investigator
Cholsoon Jang, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
There is a concerning surge in the incidence of liver cancer in Orange County. Latino populations are particularly prone to developing liver cancer, partly due to their high consumption of dietary fructose, which causes fatty liver disease and eventually leads to liver cancer. However, not all individuals who consume excessive fructose develop liver cancer, underscoring the existence of key inherent factors that increase liver cancer susceptibility. This proposal aims to identify such factors and associated molecular mechanisms, eventually to reduce liver cancer incidence for vulnerable individuals.
Estrogen-Induced Oncogenic RNA Translation in Young Women's Tumors
Investigators
Gina Lee, PhD, Department of Microbiology & Molecular Genetics, UC Irvine School of Medicine
Thomas Martinez, PhD, (Co-Investigator), Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy & Pharmaceutical Sciences
In young women of childbearing age with elevated estrogen levels, a tumor syndrome known as LAM can cause uncontrolled cell growth in the kidneys and lungs. The current therapeutic drug for LAM, rapamycin, often induces severe side effects and exhibits limited effectiveness in tumor removal. This proposal aims to elucidate a novel signaling pathway that enhances the tumorigenic growth of LAM cells, particularly in the presence of estrogen. The efficacy of a new therapeutic drug targeting this pathway will be tested in pre-clinical mouse models and patient cells. The success of this project has the potential to transform LAM treatment and offer insights into other hormone-induced women's cancers, including breast and ovarian cancers.
Peritoneal Lavage Exosomes Gene Signature in Gastric Cancer Peritoneal Carcinomatosis
Investigator
Maheswari Senthil, MD, Department of Surgery, UC Irvine School of Medicine
Gastric cancer is an aggressive cancer that often spreads to the lining of the abdominal cavity and is associated with a very high death rate. This problem disproportionately affects Latinx race/ethnic group. One of the major challenges with gastric cancer spread to abdominal cavity is lack of diagnostic studies that can accurately identify the problem and assess treatment response. We propose to study nanovesicles (exosomes) in the abdominal cavity fluid as a way to develop a diagnostic tool that can accurately identify cancer spread in the abdominal cavity and predict treatment response. We believe, study of nanovesicles will help develop a more accurate diagnostic tool and will greatly facilitate advancing treatment in patients with gastric cancer with intraabdominal spread.
Enhancing CAR T cell Activity by Eliminating Branched N-glycans
Investigator
Michael Demetriou, MD, PhD, Departments of Neurology and Microbiology & Molecular Genetics, UC Irvine School of Medicine
Prognosis is abysmal for patients with advanced solid tumors and there is an urgent unmet need for novel mechanisms of action and additional paradigm shifting therapeutic options. Genetically engineering immune cells to bind and kill cancer cells is a highly potent way of treating liquid cancers, but has been unsuccessful in solid cancers due to lack of binding targets and immunosuppression. Here we propose to address both these roadblocks by genetically engineering an immune cell that 1) targets a novel sugar-antigen expressed in the vast majority of solid cancers and 2) is resistant to immunosuppression via alterations in complex sugar-chains.
Study the Role of Mutated NF2 in Neurofibromatosis Type 2 Cancer
Investigator
Wenqi Wang, PhD, Department of Developmental and Cell Biology, UC Irvine School of Biological Sciences
Neurofibromatosis type 2 is a childhood cancer with tumors developed in brain and throughout the nervous system. This cancer is an autosomal dominant genetic disorder and majorly caused by the NF2 gene mutation, which means that the child will inherit the cancer if just one parent’s NF2 gene has a mutation. In this application, we propose to investigate an oncogenic pathway that is activated by the mutated NF2 and also required for the mutated NF2-induced cancer development. We will investigate the underlying mechanism and determine the therapeutic potential by targeting this oncogenic pathway for treating the NF2 mutated neurofibromatosis type 2 cancer.
Early Detection and Diagnosis of DNA Repair Deficient Hereditary Cancers
Investigator
Nicholas Pannunzio, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Jennifer Valerin, MD, PhD, (Co-Principal Investigator), Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Hereditary cancer syndromes are thought to drive cancer in approximately 5% of cases. Patients carrying mutations are at high risk for the development of multiple tumors at an early age. Genetic counselors are in demand and limited testing may be performed due to availability or financial resource. Additionally, the impact of these syndromes is far wider due to the effect on family members who may not even have a cancer diagnosis and don't have access to testing.
Single Molecule Dissection of Cancer-Associated Kinase Mutants
Investigator
Gregory Weiss, PhD, Department of Chemistry, UC Irvine School of Physical Sciences
Enzymes drive cell growth and cell division, and all cancers prominently feature improper enzyme activity by a class of signal transmitting enzymes, termed kinases. Thus, understanding such proteins is critically important for the development of more effective anti-cancer therapeutics. This proposal simplifies and reinvents a nanometer-scale technology for directly observing and dissecting kinases while they catalyze chemical transformations at the heart of cancer formation. This research aims to reveal targets for the development of drugs and diagnostics with novel mechanisms and capabilities.
Enhancing the Efficacy of Radiation Therapy by Surgically Targeted Radiation-Sensitizer Loaded Hydrogels: Translation of in Vitro Results to a Post-Resection Rat Brain Tumor Model
Investigator
Henry Hirschberg, PhD, The Beckman Laser Institute, UC Irvine School of Medicine
This research project has as its aim to enhance the therapeutic effects of image guided radiation therapy in the treatment of primary brain cancer. A slow-release delivery system for compounds termed radiation sensitizers, known to enhance the effects of radiation therapy, will be implanted in the cavity formed after surgical removal of a major portion of the tumor. Enhancing the site-specific ability of radiation to selectively kill tumor cells, while spearing normal tissue, would result in a higher chance of cure and reduce unwanted treatment side effects. The development of the proposed therapeutic modality would potentially not only improve the prognosis of patients suffering from primary and metastatic brain tumors but would also be applicable to other forms of operable cancer, such as breast and lung.
Characterization of the Immune Response to Neoadjuvant Anti-PD-1 and -LAG3 therapy in Stage 3 Melanoma
Investigators
Francesco Marangoni, PhD, Department of Physiology & Biophysics, UC Irvine School of Medicine
Warren Chow, MD, (Co-Principal Investigator), Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Pre-operative and post-operative immunotherapy with a single immune-activating antibody is the new standard of care for patients with locally-advanced (lymph node positive) melanoma. The addition of a second, immune activating antibody has improved outcomes for patients with metastatic melanoma. We will test the use of two immune-activating anti-PD-1 and anti-LAG3 antibodies, AND increasing the number of doses pre-operatively to improve outcomes for patients with locally-advanced melanoma. In this Anti-Cancer Challenge proposal, we will characterize and quantify the immune response in the blood at landmark time points before treatment, and after pre-operative and post-operative immunotherapy.
Innate Immune Agonist Codrugs for Cancer Immunotherapy
Investigators
Thomas Burke, PhD, Department of Microbiology and Molecular Genetics, UC Irvine School of Medicine
Vy Dong, PhD, (Co-Principal Investigator), Department of Chemistry, UC Irvine School of Physical Sciences
We are developing a new class of small molecule anti-cancer drugs that could be used to treat many cancer indications. Our approach targets the innate immune system, and thus these drugs can synergize with existing immunotherapies that activate adaptive immunity, like checkpoint inhibitors. Our efforts will aid public health by advancing novel anti-cancer drugs towards the clinic, and if successful could lead to clinical trials.
Health Disparities and Early-Onset HER2+ Breast Cancer in Vietnamese Women
Investigators
Devon Lawson, PhD, Department of Physiology and Biophysics, UC Irvine School of Medicine
Kai Kessenbrock, PhD, (Co-Principal Investigator), Department of Biological Chemistry, UC Irvine School of Medicine
Erin Lin, MD, (Co-Principal Investigator), Department of Surgery, UC Irvine School of Medicine
Robert Edwards, MD, (Co-Principal Investigator), Department of Pathology, UC Irvine School of Medicine
This proposal aims to fill the research gap regarding mechanisms of breast cancer initiation in the Vietnamese community in our catchment area in Orange County. Studies from the California Cancer Registry reveal that Vietnamese women are disproportionately affected by aggressive HER2+ breast cancer compared to non-Hispanic White women. To investigate potential biological mechanisms underlying this heightened risk, our team will utilize single-cell and spatial technologies to analyze both normal and malignant tissues from Vietnamese patients and compare them to tissues from women representing other race/ethnic groups. Our research will not only addresses a critical gap in understanding breast cancer disparities but also offers potential for tailoring treatment strategies to Vietnamese women specifically in our catchment area in OC
Regulatory Effects of Xist on the Development of Female and Male Colorectal Cancer
Investigators
Mei Kong, PhD, Department of Molecular Biology and Biochemistry, UC Irvine School of Biological Sciences
Sha Sun, PhD, (Co-Principal Investigator), Department of Developmental & Cell Biology, UC Irvine School of Biological Sciences
The proposed approach of using transgenic mouse models will set an example to address specific factors contributing to sex differences in cancer development. In precision medicine, understanding the genetic and epigenetic basis for the difference in cancer incidence between men and women will lead to the development of drugs and prevention strategies that consider a patient’s gender. The proposed research could help improve individual health outcomes by providing deeper insights into living systems.
Investigator
Brian Sworder, MD, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Immune based treatment strategies are increasingly employed to treat patients with non-Hodgkin lymphoma (NHL), but many patients still experience relapse. In this study we seek to develop of method through which we can better understand how mutations in particular genes contribute to treatment resistance following a particular type of immune based therapy called chimeric antigen receptor (CAR) T-cells. If successful, this project will build a foundation for future clinical trials by informing the development of improved immunotherapies for this illness and improve outcomes for patients.
Investigation of Microprotein Contributions to Pancreatic Ductal Adenocarcinoma
Investigator
Thomas Martinez, PhD, Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy & Pharmaceutical Sciences
The identification and characterization of all proteins encoded in the human genome is critical for understanding both normal physiology and disease. Here we will investigate how a class of previously overlooked small proteins impact tumor growth in pancreatic ductal adenocarcinoma. By uncovering novel regulators of tumor growth, we hope to enable the discovery of targeted therapeutics and biomarkers for early diagnosis of this incredibly lethal disease.
Targeting Neoplastic Cell Fate Transitions Through Adhesome Signaling
Investigator
Timothy Downing, PhD, Department of Microbiology & Molecular Genetics, UC Irvine School of Medicine
Our research aims to develop a groundbreaking platform technology that can reveal how cancer cells change over time and in response to treatment. By studying these changes, we hope to identify new ways to treat cancer more effectively and prevent relapse. This innovative approach could lead to personalized treatment options and ultimately improve outcomes and overcome health disparities for cancer patients in our community and around the world.
Exploring Lipid Metabolism in NAFLD-HCC Transition Using Stem Cell Derived Hepatocytes
Investigator
Quinton Smith, PhD, Department of Chemical and Biomolecular Engineering, UC Irvine Samueli School of Engineering
Our research investigates how changes in fat processing within liver cells contribute to the development of liver cancer. We aim to understand how exposure to certain fats, similar to those associated with a common liver disease called NAFLD, affects the behavior of liver cells derived from stem cells. By studying this, we hope to uncover the underlying mechanisms that drive liver cancer development from metabolic dysfunction. Additionally, we will use advanced genetic techniques to introduce specific genetic changes associated with a higher risk of liver disease found in Hispanic populations, to shed light on how genetic factors influencing likelihood of cancer development.
Innovative Approaches to Address Chemoresistance in Prostate Cancer: Integrating Electrokinetic and Microfluidic Technologies
Investigator
Tayloria Adams, PhD, Department of Chemical and Biomolecular Engineering, UC Irvine Samueli School of Engineering
Our research project aims to develop innovative methods to combat chemoresistance in prostate cancer, a disease that disproportionately affects African American men, who experience higher rates of incidence and mortality. By utilizing advanced engineering techniques to study the physical properties of cancer cells and their response to treatment, we seek to understand the underlying mechanisms of chemoresistance. This research is crucial for addressing health disparities and enhancing our understanding of prostate cancer biology, leading to the development of targeted therapeutic interventions. Ultimately, our findings could lead to improved treatment strategies for all individuals affected by prostate cancer, particularly those from marginalized communities, potentially extending and enhancing their quality of life.
Financial Implications of a Pediatric/Adolescent/Young Adult (AYA) Cancer Diagnosis on a Patient’s Quality of Life and Health Outcomes
Investigator
Sonia Morales, MD, MPH, Department of Pediatrics, UC Irvine School of Medicine
Pediatric and adolescent/young adult (AYA) cancer survivors, along with their families, often face financial hardships. To evaluate the health outcomes and financial implications on pediatric/AYA patients with cancer and their parents, longitudinal data is needed, particularly in a culturally diverse population. This study seeks to investigate and characterize how financial hardship correlates to decreased care nonadherence, increased psychological distress and educational/vocational status among pediatric/AYA cancer patients.
HMGB2 Regulation of Anti-Tumor T cell Immunity
Investigator
Roberto Tinoco, PhD, Department of Molecular Biology and Biochemistry, UC Irvine School of Biological Sciences
Few cancer patients respond to current immunotherapies, highlighting the pressing need to identify, develop, and improve treatments that are efficient and safe for patients that presently have no treatment options. The proposed studies will determine whether a new protein in T cells is essential for their ability to kill cancer cells. If successful, the study may lead to new drugs that may improve therapies for cancer patients.
A Novel Gut-Liver Axis as a Risk Factor for Liver Cancer
Investigator
Cholsoon Jang, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
There is a concerning surge in the incidence of liver cancer in Orange County. Latino populations are particularly prone to developing liver cancer, partly due to their high consumption of dietary fructose, which causes fatty liver disease and eventually leads to liver cancer. However, not all individuals who consume excessive fructose develop liver cancer, underscoring the existence of key inherent factors that increase liver cancer susceptibility. This proposal aims to identify such factors and associated molecular mechanisms, eventually to reduce liver cancer incidence for vulnerable individuals.
Estrogen-Induced Oncogenic RNA Translation in Young Women's Tumors
Investigators
Gina Lee, PhD, Department of Microbiology & Molecular Genetics, UC Irvine School of Medicine
Thomas Martinez, PhD, (Co-Investigator), Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy & Pharmaceutical Sciences
In young women of childbearing age with elevated estrogen levels, a tumor syndrome known as LAM can cause uncontrolled cell growth in the kidneys and lungs. The current therapeutic drug for LAM, rapamycin, often induces severe side effects and exhibits limited effectiveness in tumor removal. This proposal aims to elucidate a novel signaling pathway that enhances the tumorigenic growth of LAM cells, particularly in the presence of estrogen. The efficacy of a new therapeutic drug targeting this pathway will be tested in pre-clinical mouse models and patient cells. The success of this project has the potential to transform LAM treatment and offer insights into other hormone-induced women's cancers, including breast and ovarian cancers.
Peritoneal Lavage Exosomes Gene Signature in Gastric Cancer Peritoneal Carcinomatosis
Investigator
Maheswari Senthil, MD, Department of Surgery, UC Irvine School of Medicine
Gastric cancer is an aggressive cancer that often spreads to the lining of the abdominal cavity and is associated with a very high death rate. This problem disproportionately affects Latinx race/ethnic group. One of the major challenges with gastric cancer spread to abdominal cavity is lack of diagnostic studies that can accurately identify the problem and assess treatment response. We propose to study nanovesicles (exosomes) in the abdominal cavity fluid as a way to develop a diagnostic tool that can accurately identify cancer spread in the abdominal cavity and predict treatment response. We believe, study of nanovesicles will help develop a more accurate diagnostic tool and will greatly facilitate advancing treatment in patients with gastric cancer with intraabdominal spread.
Enhancing CAR T cell Activity by Eliminating Branched N-glycans
Investigator
Michael Demetriou, MD, PhD, Departments of Neurology and Microbiology & Molecular Genetics, UC Irvine School of Medicine
Prognosis is abysmal for patients with advanced solid tumors and there is an urgent unmet need for novel mechanisms of action and additional paradigm shifting therapeutic options. Genetically engineering immune cells to bind and kill cancer cells is a highly potent way of treating liquid cancers, but has been unsuccessful in solid cancers due to lack of binding targets and immunosuppression. Here we propose to address both these roadblocks by genetically engineering an immune cell that 1) targets a novel sugar-antigen expressed in the vast majority of solid cancers and 2) is resistant to immunosuppression via alterations in complex sugar-chains.
Study the Role of Mutated NF2 in Neurofibromatosis Type 2 Cancer
Investigator
Wenqi Wang, PhD, Department of Developmental and Cell Biology, UC Irvine School of Biological Sciences
Neurofibromatosis type 2 is a childhood cancer with tumors developed in brain and throughout the nervous system. This cancer is an autosomal dominant genetic disorder and majorly caused by the NF2 gene mutation, which means that the child will inherit the cancer if just one parent’s NF2 gene has a mutation. In this application, we propose to investigate an oncogenic pathway that is activated by the mutated NF2 and also required for the mutated NF2-induced cancer development. We will investigate the underlying mechanism and determine the therapeutic potential by targeting this oncogenic pathway for treating the NF2 mutated neurofibromatosis type 2 cancer.
Early Detection and Diagnosis of DNA Repair Deficient Hereditary Cancers
Investigator
Nicholas Pannunzio, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Jennifer Valerin, MD, PhD, (Co-Principal Investigator), Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Hereditary cancer syndromes are thought to drive cancer in approximately 5% of cases. Patients carrying mutations are at high risk for the development of multiple tumors at an early age. Genetic counselors are in demand and limited testing may be performed due to availability or financial resource. Additionally, the impact of these syndromes is far wider due to the effect on family members who may not even have a cancer diagnosis and don't have access to testing.
Single Molecule Dissection of Cancer-Associated Kinase Mutants
Investigator
Gregory Weiss, PhD, Department of Chemistry, UC Irvine School of Physical Sciences
Enzymes drive cell growth and cell division, and all cancers prominently feature improper enzyme activity by a class of signal transmitting enzymes, termed kinases. Thus, understanding such proteins is critically important for the development of more effective anti-cancer therapeutics. This proposal simplifies and reinvents a nanometer-scale technology for directly observing and dissecting kinases while they catalyze chemical transformations at the heart of cancer formation. This research aims to reveal targets for the development of drugs and diagnostics with novel mechanisms and capabilities.
Enhancing the Efficacy of Radiation Therapy by Surgically Targeted Radiation-Sensitizer Loaded Hydrogels: Translation of in Vitro Results to a Post-Resection Rat Brain Tumor Model
Investigator
Henry Hirschberg, PhD, The Beckman Laser Institute, UC Irvine School of Medicine
This research project has as its aim to enhance the therapeutic effects of image guided radiation therapy in the treatment of primary brain cancer. A slow-release delivery system for compounds termed radiation sensitizers, known to enhance the effects of radiation therapy, will be implanted in the cavity formed after surgical removal of a major portion of the tumor. Enhancing the site-specific ability of radiation to selectively kill tumor cells, while spearing normal tissue, would result in a higher chance of cure and reduce unwanted treatment side effects. The development of the proposed therapeutic modality would potentially not only improve the prognosis of patients suffering from primary and metastatic brain tumors but would also be applicable to other forms of operable cancer, such as breast and lung.
Characterization of the Immune Response to Neoadjuvant Anti-PD-1 and -LAG3 therapy in Stage 3 Melanoma
Investigators
Francesco Marangoni, PhD, Department of Physiology & Biophysics, UC Irvine School of Medicine
Warren Chow, MD, (Co-Principal Investigator), Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Pre-operative and post-operative immunotherapy with a single immune-activating antibody is the new standard of care for patients with locally-advanced (lymph node positive) melanoma. The addition of a second, immune activating antibody has improved outcomes for patients with metastatic melanoma. We will test the use of two immune-activating anti-PD-1 and anti-LAG3 antibodies, AND increasing the number of doses pre-operatively to improve outcomes for patients with locally-advanced melanoma. In this Anti-Cancer Challenge proposal, we will characterize and quantify the immune response in the blood at landmark time points before treatment, and after pre-operative and post-operative immunotherapy.
Innate Immune Agonist Codrugs for Cancer Immunotherapy
Investigators
Thomas Burke, PhD, Department of Microbiology and Molecular Genetics, UC Irvine School of Medicine
Vy Dong, PhD, (Co-Principal Investigator), Department of Chemistry, UC Irvine School of Physical Sciences
We are developing a new class of small molecule anti-cancer drugs that could be used to treat many cancer indications. Our approach targets the innate immune system, and thus these drugs can synergize with existing immunotherapies that activate adaptive immunity, like checkpoint inhibitors. Our efforts will aid public health by advancing novel anti-cancer drugs towards the clinic, and if successful could lead to clinical trials.
Health Disparities and Early-Onset HER2+ Breast Cancer in Vietnamese Women
Investigators
Devon Lawson, PhD, Department of Physiology and Biophysics, UC Irvine School of Medicine
Kai Kessenbrock, PhD, (Co-Principal Investigator), Department of Biological Chemistry, UC Irvine School of Medicine
Erin Lin, MD, (Co-Principal Investigator), Department of Surgery, UC Irvine School of Medicine
Robert Edwards, MD, (Co-Principal Investigator), Department of Pathology, UC Irvine School of Medicine
This proposal aims to fill the research gap regarding mechanisms of breast cancer initiation in the Vietnamese community in our catchment area in Orange County. Studies from the California Cancer Registry reveal that Vietnamese women are disproportionately affected by aggressive HER2+ breast cancer compared to non-Hispanic White women. To investigate potential biological mechanisms underlying this heightened risk, our team will utilize single-cell and spatial technologies to analyze both normal and malignant tissues from Vietnamese patients and compare them to tissues from women representing other race/ethnic groups. Our research will not only addresses a critical gap in understanding breast cancer disparities but also offers potential for tailoring treatment strategies to Vietnamese women specifically in our catchment area in OC
Regulatory Effects of Xist on the Development of Female and Male Colorectal Cancer
Investigators
Mei Kong, PhD, Department of Molecular Biology and Biochemistry, UC Irvine School of Biological Sciences
Sha Sun, PhD, (Co-Principal Investigator), Department of Developmental & Cell Biology, UC Irvine School of Biological Sciences
The proposed approach of using transgenic mouse models will set an example to address specific factors contributing to sex differences in cancer development. In precision medicine, understanding the genetic and epigenetic basis for the difference in cancer incidence between men and women will lead to the development of drugs and prevention strategies that consider a patient’s gender. The proposed research could help improve individual health outcomes by providing deeper insights into living systems.
TRACK 2: EARLY PHASE CLINICAL TRIALS
Phase IB, Open-Label Trial of Dual Cytotoxic and Immune-Stimulatory Gene Therapy in Combination with G-CSF for the Treatment of Resectable, Recurrent Glioblastoma (GBM)
Investigator
Daniela Bota, MD, PhD, Department of Neurology, UC Irvine School of Medicine
GBM is one of the hardest cancers to treat, with an average survival of 12-18 months. The patients receive surgery, radiation, and chemotherapy (temozolomide), but the tumors resume growth and progression after 7-9 months. There are no effective treatments for patients who experience tumor growth after the initial treatment. In California, about 1,700 people were diagnosed with GBM, and 1,200 succumbed to the disease in 2023. The GBM diagnosis is associated with severe neurological disability, reduced quality of life, and high levels of stress for the patients and their caregivers. The healthcare cost of treating one GBM patient is more than $450,000 and can reach $700,000. Finding a potential treatment for this deadly disease would benefit California patients, caregivers, and the state-supported healthcare system.
Repurposing Riluzole for Augmenting Brain-Derived Neuropathic Factor (BDNF) Levels and Cognitive Function in Breast Cancer Patients Experiencing Cancer-Related Cognitive Impairment: An Interventional Pilot Clinical Trial
Investigators
Alexandre Chan, PharmD, MPH, Department of Clinical Pharmacy Practice, UC Irvine School of Pharmacy & Pharmaceutical Sciences
Ritesh Parajuli, MD, (Co-Investigator) Division of Hematology Oncology, Department of Medicine, UC Irvine School of Medicine
Breast cancer is highly curable, yet up to 75% of breast cancer survivors in the community experience various levels of impaired cognition even many months after cancer free. Our clinical trial is evaluating a drug that may provide symptomatic relief to these survivors who are having difficulty incorporating back into the community, in view of their symptoms and reduced quality of life.
Epcoritamab Consolidation in Patients with Chronic Lymphocytic Leukemia Who Are in Remission on Continuous BTK Inhibitors
Investigators
Catherine Coombs, MD, Department of Medicine, UC Irvine School of Medicine
Susan O’Brien, MD, (Co-Investigator) Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
The most prescribed agents for patients with chronic lymphocytic leukemia (CLL) are Bruton tyrosine kinase inhibitors (BTKi), which are used continuously. However, in surveys of CLL patients, the majority of patients express a preference for time-limited regimens, especially when considering the cost of continuous therapy. Cost can be financial but may also be related to a detriment in quality of life, as BTKi may cause chronic toxicities. As such, conversion from a continuous treat-to-progression approach for patients who are on BTKi to a time-limited approach would be of interest to many patients. As epcoritamab has exhibited impressive efficacy as a single agent, the addition of epcoritamab to patients who are in a clinical remission while on a BTKi would likely led to high proportion deep remissions that would then allow for a treatment-free remission.
Adjuvant Sacituzumab Govitecan plus Nivolumab in Patients with Muscle-Invasive Urothelial Carcinoma at High-Risk for Cancer Recurrence who are ctDNA positive
Investigator
Nataliya Mar, MD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
The prognosis of metastatic urothelial carcinoma of the bladder, ureter and kidney remains poor, with only 7.7% of patients being alive at 5 years from diagnosis. As such, better treatment options are needed to prevent development of cancer returning/relapsing following surgery aimed to cure localized urothelial cancer. This study aims to evaluate the effectiveness and safety of combination therapy with Sacituzumab Govitecan and Nivolumab in patients with muscle-invasive urothelial carcinoma and minimal residual disease as detected by positive ctDNA, who are at high risk of cancer recurrence post-curative intent surgery.
