Defining and Predicting Psychosocial Risk After Surgical Treatment and Reconstruction of Melanoma
Investigator
Miles J. Pfaff, MD, Department of Plastic Surgery, UC Irvine School of Medicine
Cutaneous melanoma often requires surgery and reconstruction, which can affect patients’ appearance, recovery, and overall well-being. This study will follow patients over time to understand how treatment influences anxiety, stress, and quality of life and will identify factors that place some individuals at higher risk
for psychosocial challenges after surgery. The findings will help clinicians better counsel patients and develop targeted support strategies to improve recovery and patient-centered outcomes, particularly in Orange County, where melanoma incidence and mortality are higher among certain populations, including non-Hispanic White females, non-Hispanic White males, and Hispanic/Latino males. A patient stakeholder with lived experience of melanoma surgery will also participate in study design and interpretation of patient reported outcomes, strengthening the patient-centered relevance of the research and supporting future potential PCORI-focused patient engagement efforts.
Investigating the impact of PFAS exposure via drinking water on ovarian cancer outcomes
Investigator
Carolina Villanueva, MPH, PhD, Department of Environmental and Occupational Health, UC Irvine Joe C. Wen School of Population and Public Health
The respective pilot project will examine whether exposure to chemicals known as per and polyfluoroalkyl substances (PFAS) in drinking water are associated with ovarian cancer (OC) survival among women diagnosed in California and determine who may be more susceptible to their effects. PFAS are found widely in the environment and are present in nearly everyone’s blood. With increasing evidence of their negative health effects and recent reports that more than 200 million Americans are served by drinking water with detected PFAS levels, they present a serious public health concern. Considering the poor prognosis of OC, the extent of PFAS exposures, and drinking water regulations that are currently shifting, this study will provide much needed evidence of the potential impact of PFAS on OC survival, responsiveness to treatment, and possible contributions to disparities in outcomes.
A New Strategy to Kill Kinase Inhibitor Resistant Tumors
Investigator
Anand Ganesan, MD, Department of Dermatology, UC Irvine School of Medicine
Small molecule inhibitors that target kinase mutations observed in cancer can rapidly shrink tumors with the relevant mutations, but these tumors can recur rapidly (< 6 months) by activating signaling loops that bypass the effects of kinase inhibitors. Kinase inhibitor resistant tumors are no longer responsive to either kinase inhibitor therapies or immunotherapies, and new approaches are needed to prevent resistance/ treat resistant tumors. UCI-developed drugs that target CDC42 signaling can block signaling loops activated in resistant tumors, identifying a new way to treat kinase inhibitor resistant tumors. We uncover how CDC42 inhibitors developed by our group kill kinase inhibitor resistant tumors and identify CDC42 signaling pathways that are amplified in kinase inhibitor resistant human tumors.
Reducing Avoidable Emergency Department Use Among Cancer Patients in Safety-Net Hospitals
Investigator
Annie Ro, PhD, Department of Health, UC Irvine Joe C. Wen School of Population & Public Health
Many cancer patients visit the emergency room for issues that could be better handled in a regular doctor's office. Regular use of the emergency room can lead to higher costs for hospital systems and worse outcomes for these patients. Our project uses local health data from Los Angeles County to understand why this happens, focusing on how factors like housing, language, and insurance status raise a cancer patient's risk to use the ED when they don’t have to. We plan to develop a predictive tool to help clinicians identify high-risk patients early so they can provide extra support and navigation services. This work aims to make cancer treatment more efficient, especially for patients who get their medical care in the safety-net system.
Q-CODE: Quality of Life with Combined Estrogen Patch and Darolutamide in Metastatic Hormone-Sensitive Prostate Cancer
Investigator
Arash Rezazadeh, MD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Current treatments for advanced prostate cancer are effective but often cause significant side effects that reduce patients’ energy, physical strength, and overall quality of life. This study tests a new approach that uses an estrogen patch instead of standard hormone therapy, combined with a well-tolerated medication (darolutamide), to treat the cancer while reducing these side effects. By preserving important hormones in the body, this strategy may help patients maintain their daily functioning and feel better during treatment. If successful, this research could lead to safer, more patient-centered treatments and support larger future clinical trials.
Synergistic Immunomodulation in Pancreatic Ductal Adenocarcinoma using cDC1 Vaccines, COX-2 Inhibition, and CIML NK Cells
Investigator
Aydin Eresen, PhD, Department of Radiological Sciences, UC Irvine School of Medicine
Pancreatic cancer is exceptionally difficult to treat because the tumor creates a protective “shield” that prevents the body’s immune system from attacking it. This project tests a new combination therapy designed to break down that shield using an anti-inflammatory drug, while simultaneously training the immune system with a specialized vaccine and enhanced immune cells to find and destroy the tumor. By also using advanced MRI scans to monitor the treatment's success without needing invasive biopsies, this pilot study will provide the essential data needed to secure federal funding for larger studies, ultimately paving the way for new clinical trials for pancreatic cancer patients.
Developing a Functional Immune-oncology Platform for Pancreatic Ductal Adenocarcinoma
Investigators
Christopher Halbrook, PhD, Department of Molecular Biology and Biochemistry, UC Irvine Charlie Dunlop School of Biological Sciences
Lisa Wagar, PhD, Department of Physiology & Biophysics, UC Irvine School of Medicine
Pancreatic cancer is one of the deadliest cancers and is especially difficult to treat because the immune system cannot effectively attack the tumor. This project develops a new laboratory model using patient tumor and immune tissues to better understand how pancreatic cancer suppresses immune responses. By testing immunotherapies and nanoparticle-based treatments in this system, the research aims to identify strategies that could make treatments more effective. Ultimately, this work could help guide the development of new therapies to improve survival for patients with pancreatic cancer.
Evaluating tumor microenvironment-mediated radioprotection and FLASH radiotherapy in an in-vitro vascularized model of cervical cancer
Investigator
Christopher C.W. Hughes, PhD, Department of Molecular Biology and Biochemistry, UC Irvine Charlie Dunlop School of Biological Sciences
Cervical cancer remains a significant cause of cancer-related deaths in women worldwide, and while radiotherapy is a cornerstone of treatment, the tumor microenvironment - including factors like poor oxygenation and complex cellular interactions - can actively shield cancer cells from radiation, limiting treatment effectiveness. Standard 2D cell culture models often fail to capture these protective features, making it difficult to predict how new treatment strategies will perform in patients. Our research utilizes an innovative “organ-on-a-chip” technology to create a miniature, human cell-based vascularized 3D model of cervical cancer that closely mimics the complex tumor environment in the human body, allowing us to study how the tumor microenvironment influences radiation response. Using this advanced platform, we will investigate whether FLASH radiotherapy - an emerging technique that delivers radiation at ultra-high dose rates - can overcome these microenvironmental barriers while also sparing surrounding healthy tissue; potentially offering a safer and more effective alternative to conventional radiotherapy for patients with cervical cancer.
Development of an Intelligent Chatbot to Aid Quit-Smoking Support Groups
Investigator
Connie (Cornelia) Pechmann, PhD, MBA, MS, UC Irvine Paul Merage School of Business
This research aims to enhance the performance of a chatbot to assist individuals in small, private, online, peer- support groups for quitting smoking, addressing the challenge of providing rapid responses when human members are unavailable. The chatbot, driven by Artificial Intelligence (AI), identifies the common post types or topics discussed in the support groups and generates a variety of engaging responses. This project aims to enhance the accuracy, relevance, and safety of chatbot-generated responses through retrieval-augmented generation (RAG) to select the most relevant candidate responses, the testing of multiple strategies to optimize the final responses, and the detection and minimization of hallucination responses by cross-referencing with authoritative medical sources. Improved chatbot responses will increase engagement in the support groups, both peer-to-chatbot and peer-to-peer, thus improving quit rates, with significant implications for public health
Expanding the Degradome of Bypassing E-Ligase Targeting Chimera (ByeTACs)
Investigator
Darci J. Trader, PhD, Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy and Pharmaceutical Sciences
ByeTACs (Bypassing E3-Ligase Targeting Chimeras) are a new type of drug design that helps cells remove harmful proteins. Instead of relying on the established protein tagging system, ByeTAC molecules bring a disease-causing protein directly to the cell’s degradation machinery, called the proteasome, so it can be broken down and removed. This strategy can bypass biological steps that limit many current protein-degrading drugs and may allow for targeting proteins that were previously difficult to eliminate. By directly guiding unwanted proteins to destruction, ByeTACs could open new possibilities for treating diseases such as cancer, neurological disorders, as well as infectious diseases.
Leveraging Telomere Biology in Pathobiology and Treatment of Myeloproliferative Neoplasms
Investigator
Feng Qiao, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
Myeloproliferative neoplasms (MPNs) are common blood cancers in which abnormal blood cells overgrow due to genetic mutations that can arise decades before patients are diagnosed, yet it remains unclear why some people develop aggressive disease while others do not. This project investigates whether the length of telomeres — the protective caps on the ends of chromosomes that shorten as cells divide and age — plays a key role in determining which blood cancer-driving mutations survive and expand over a lifetime, by using advanced DNA sequencing to identify genetic variants in telomere-regulating genes across MPN patients of different ages. If successful, this research could lead to a simple blood test that measures telomere biology at diagnosis to guide doctors in choosing the most effective therapy for each individual patient, moving MPN treatment from a one-size-fits-all approach toward personalized, precision medicine.
The role of natural immunity in modulating antitumor T cell responses
Investigator
Francesco Marangoni, PhD, Department of Physiology & Biophysics, UC Irvine School of Medicine
Elevated hygiene levels in highly developed countries may increase the incidence of tumors. In this Anti-Cancer Challenge proposal, we will use mouse models bearing a variety of natural microbes at all barrier surfaces to study the mechanisms linking the continuous exposure to microorganisms and protection from melanoma, which is a highly prevalent cancer in our catchment area. Our research will pave the way to medical interventions or public health strategies to decrease tumor incidence in highly developed nations.
LIFT: Lifestyle Improvement to Facilitate Tumor-immunity
Investigator
Gary Deng, MD, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Immunotherapy can eliminate all detectable cancer before surgery in patients with melanoma or bladder cancer, but this occurs in fewer than half of patients and the reasons are not well understood. The LIFT study will investigate whether a patient’s everyday behaviors—physical activity, sleep, stress, and diet— influence how well a patient’s immune system responds to immunotherapy, using a fitness tracker and smartphone app to monitor these behaviors throughout treatment while tumor tissue and blood are analyzed before and after therapy. If specific lifestyle factors emerge as meaningful predictors, this research will pinpoint the intervention targets for a larger clinical trial testing whether helping patients adopt healthier lifestyle habits during treatment can improve cancer outcomes.
ACCESS-LCS: Adjunctive Cheek Cell Evaluation Using Spectroscopy to Enhance Risk Stratification in Lung Cancer Screening
Investigator
Gelareh Sadigh, MD, Department of Radiological Sciences, UC Irvine School of Medicine
Adherence to lung cancer screening with low dose computed tomography remains low with multiple contributing patient-, provider-, and system-level barriers. Our study will assess the feasibility and acceptability of check swab-based test for lung cancer screening and patients’ and providers’ preferences for this test compared to low dose computed tomography. We will further explore agreement rate between the two tests as well as cancer rate and follow-up test utilization among patients with discordant test results. Because cheek swab collection is simple, and easily integrated into routine primary care workflows, it may also reduce structural barriers and expand access to screening, particularly in underserved populations.
Targeting the RNA Exosome to Induce Immunogenic RNA Stress and Enhance Cancer Immunotherapy
Investigator
Ivan Marazzi, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
The RNA exosome is a cellular system that removes faulty or excess RNA to maintain cell health. When this system is disrupted, abnormal RNA accumulates and can trigger immune responses that help the body recognize cancer cells. This project will investigate whether blocking the RNA exosome can enhance these immune signals and improve responses to immunotherapy. This approach may offer a new treatment strategy for cancers that currently do not respond well to existing therapies, such as lung cancer, melanoma, and triple- negative breast cancer.
Human ILC2s Orchestrate Antitumor Immunity via Cytotoxicity and Nonconventional Antigen Presentation to CD8 T Cells
Investigator
Jianhua Yu, PhD, Department of Medicine, UC Irvine School of Medicine
We study a special type of immune cell in the human body called ILC2s and recently found that these cells can directly kill tumor cells. The current project aims to understand how ILC2s work specifically with “killer” T cells to recognize and destroy cancer cells. Our research focuses on how ILC2s communicate with and activate killer
T cells, helping them persist longer and respond more effectively to tumors. By understanding how ILC2s and killer T cells work together, this research may lead to new ways to treat cancer and strengthen the body’s natural ability to fight it.
The role of donor sleep on allo-HSCT immune reconstitution and outcomes.
Investigator
Katharine Simon, PhD, Department of Pediatrics, UC Irvine School of Medicine
Stem cell transplantation is a life-saving treatment for a broad spectrum of malignant and non-malignant blood conditions, but the success of treatment depends heavily on the quality of the stem cells. This study examines whether donor’s sleep in the weeks prior to donation affects how well the stem cells work. By tracking sleep with wearable devices, we aim to identify sleep as a simple, low-risk way to improve transplant outcomes. Given that sleep is readily modifiable, our findings have the potential to inform practical recommendations that improve increase stem cell quality and increase the likelihood of successful stem cell transplantation.
Methionine Restriction and the Epitranscriptome in Cancer
Investigator
Klemens Hertel, PhD, Department of Microbiology & Molecular Genetics, UC Irvine School of Medicine
Cancer cells have a unique weakness: they depend heavily on the amino acid methionine to grow and divide, while healthy cells can manage without it by using a similar building block called homocysteine. This pilot project will use cutting-edge technology to examine how reducing methionine changes small chemical methylation marks that are added to RNA molecules in the cell. These marks help control how RNA is processed and used to make proteins, and our work aims to show if low methionine disrupts these marks in ways that interfere with normal RNA handling, ultimately slowing cancer growth. By revealing these molecular links, the research could pave the way for new therapies combining dietary restrictions with targeted drugs, improving cancer treatment outcomes and reducing side effects for patients.
Depression Phenotype and Organ-Specific Aging in Cancer Caregivers
Investigator
Michael A. Hoyt, PhD, Department of Global Health and Biobehavioral Sciences, UC Irvine Joe C. Wen School of Population & Public Health
Family members who care for loved ones with cancer often experience chronic stress, sleep loss, and emotional exhaustion that can quietly take a toll on their own health. This study examines whether these caregiving demands speed up biological aging in specific organs—such as the heart, brain, and immune system—using advanced blood-based markers. By linking changes in mood, fatigue, and sleep to measurable changes in the body, this research will help explain how caregiving stress “gets under the skin.” Findings will inform future interventions designed to protect the long-term health and well-being of the millions of family caregivers who are essential to cancer care.
Epithelioid models for cell competition
Investigator
Nicholas Baker, PhD, Department of Developmental & Cell Biology, UC Irvine Charlie Dunlop School of Biological Sciences
This is a project to evaluate the possibility that tissues have an intrinsic defense mechanism against cancer called cell competition, and develop a method for studying it using mouse esophageal cells. Cell competition would eliminate potential cancer cells by recognizing large chromosome differences from normal cells. This could be part of the body’s defense against many cancers including common cancers such as breast and colon. An experimental model for cell competition developed using mouse cells will enable studies aiming to enhance cell competition in cancer prevention, and obtain better understanding of how cell competition sometimes fails and allows cancers to develop.
Exploring Diet-Drug Synergy to Potentiate PRMT5 Inhibitors in Glioblastoma
Investigator
Peter Kaiser, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
This project will explore whether specific dietary changes can improve the effectiveness of new drugs that target PRMT5, a protein important for the growth of glioblastoma, an aggressive brain cancer. By testing these strategies in human glioblastoma cells and intracranial xenograft mouse models, the work will
determine whether diet can safely make cancer cells more vulnerable to treatment. The findings could identify simple, nutrition-based approaches that enhance current therapies without adding significant toxicity. Ultimately, this research aims to lay the groundwork for more effective, personalized treatment strategies that improve outcomes for patients with glioblastoma.
Epigenetic Reprogramming of iPSC-derived CAR T Cells to Enhance Functional Persistence
Investigator
Ran Jing, PhD, Department of Biological Chemistry, UC Irvine School of Medicine
CAR T cell therapy is a powerful cancer treatment, but it is currently limited by cost, manufacturing time, and the need for patient-specific cells. Our research aims to develop a more accessible “off-the-shelf” therapy by using stem cells to generate immune cells in the lab. We are identifying small molecules that help these cells stay active, grow well, and resist exhaustion when fighting cancer. This work has the potential to make life- saving immunotherapies more effective, scalable, and available to a broader range of patients.
Combinatorial targeting of ferroptosis in TNBC: A pilot study in vitro
Investigator
Richard Van Etten, MD, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Triple-negative breast cancer (TNBC) is CFCCC catchment area priority cancer whose current therapy is inadequate. TNBC has been shown to be uniquely sensitive to agents that induce a process known as ferroptosis, where iron in the cell triggers membrane damage and cell death. This research will explore whether combinations of existing drugs that enhance ferroptosis could work together, increasing the anti-cancer effect while minimizing toxicity. The results of the research could trigger further studies aimed at developing new therapeutic approaches targeting ferroptosis for TNBC and other hard-to-treat solid tumors including pancreatic adenocarcinoma and glioblastoma.
Reinvigorating melanoma anti-tumor immunity by inhibiting PSGL-1 immune checkpoints on myeloid cells
Investigator
Roberto Tinoco, PhD, Department of Molecular Biology and Biochemistry, UC Irvine Charlie Dunlop School of Biological Sciences
This research focuses on a specific molecule called P-selectin glycoprotein ligand-1 (PSGL-1), found on myeloid cells. We believe PSGL-1 may play a significant role in dampening immune responses against melanoma, allowing tumors to grow more effectively. Our preliminary findings show that PSGL-1 is highly expressed on myeloid cells within melanoma tumors. In experiments with mice lacking PSGL-1 in these immune cells, we observed better control of tumor growth and stronger immune responses.Overall, this study aims to clarify the role of PSGL-1 in myeloid cells, potentially leading to novel treatments that improve the immune system’s ability to combat melanoma. By targeting this molecule, we hope to develop strategies that can enhance anti-tumor immunity, offering new hope for patients with limited treatment options.
Discovery of Molecular and Cellular Biomarkers for the Malignant Transformation of Conjunctival Melanocytic Intraepithelial Lesions
Investigator
Rui Chen, PhD, Department of Ophthalmology, UC Irvine School of Medicine
Melanocytic neoplasms are not always unequivocally classified as either benign or malignant. A subset of intermediate lesions, usually detected by histologic assessment, demonstrate ambiguous morphological features, requiring molecular analysis for further characterization. We propose to identify early molecular alterations and cellular biomarkers to improve the classification of C-MIL and determine the risk of malignant transformation.
Targeting Piezo1 Channels to Improve CD8 T Cell-mediated Solid Tumor Immunity
Investigator
Shivashankar Othy, PhD, Department of Physiology and Biophysics, UC Irvine School of Medicine
Solid tumors, which make up the vast majority (~90%) of adult cancers, are challenging to attack using immunotherapies because the stiff tissue environment excludes immune cells and limits their ability to kill tumor cells. Our project is highly relevant to cancer research because we will define the fundamental mechanisms by which CD8 T cells (essential tumor-killing cells) sense and respond to the mechanical properties of solid tumors. Our studies will evaluate Piezo1, a mechanosensing ion channel, as a potential therapeutic target (mechanical checkpoint) to overcome barriers to CD8 T cell function in stiff tissues, with broad applicability across various forms of solid tumors affecting people from all backgrounds, ethnicities, and socioeconomic statuses. In the big picture, a better understanding of the role of biomechanical signals in regulating the immune system in solid tumors will transform the rapidly evolving cancer immunotherapies and improve the quality of life of millions of individuals with solid cancers.
Sleep Health among Young Adult Cancer Survivors
Investigator
Sunmin Lee, PhD, Department of Medicine, UC Irvine School of Medicine
This pilot study will generate critical preliminary data to guide future sleep intervention study among young adult cancer survivors in Southern California. Results will help identify the prevalence of sleep disturbance, specific sleep-related late effects that may disproportionately affect this population and provide an in-depth understanding of sleep difficulties.
Robotic-Guided Optical Coherence Tomography for Real-Time Evaluation of Peripheral Pulmonary Nodules in Early Lung Cancer Detection
Investigators
Thomas W Waddington, MD, Department of Medicine, UC Irvine School of Medicine
Zhongping Chen, PhD, Department of Biomedical Engineering, UC Irvine Samueli School of Engineering
Lung cancer remains the leading cause of cancer-related death, and many patients undergo invasive biopsies to determine whether a lung nodule is cancerous. Current imaging methods can locate nodules but cannot provide detailed structural information before tissue is removed, exposing patients to risks such as bleeding or lung collapse. This project will integrate a high-resolution optical imaging technology with robotic bronchoscopy to allow physicians to visualize microscopic tissue features in real time during evaluation. By improving early and more precise assessment of lung nodules, this approach may reduce unnecessary procedures and enhance the safety and accuracy of lung cancer diagnosis
Feasibility Study of Long-Term Adolescent/Young Adult Hodgkin Lymphoma Survivors
Investigator
Wendy Cozen, DO, MPH, , Department of Medicine, UC Irvine School of Medicine
This proposal has community relevance for providing pilot data for a larger R01 grant to understand and mitigate late effects that can negatively impact the quality of life of long-term adolescent/young adult Hodgkin lymphoma survivors. We will also test samples that were collected near the time of diagnosis (up to 18 years ago) to determine if they are still viable for additional studies to evaluate immune function and its impact on late effects. Results will provide critical information to leverage samples and data collected for a study decades ago, to identify determinants at or near the time of diagnosis of future adverse late effects among long-term survivors. AYA cancers and survivorship are priority areas for the CFCCC, and this proposal addresses these topics with a novel resource and new Cancer Control Program collaborations.
Establishing a spatial-genomics based cancer neuroscience platform to map neural–tumor interactions in human cancers
Investigator
Xiangmin Xu, PhD, Department of Anatomy & Neurobiology, UC Irvine School of Medicine
Cancer remains a major health challenge in Orange County and beyond; improving early diagnosis and treatment are critical for better patient outcomes. This project will develop new approaches to study how cancer cells interact with neural elements within tumors, an emerging area of research that may influence how cancers grow and respond to treatment – and will impact UCI Health patients first as this knowledge is generated here. By applying advanced spatial genomics technologies to tumor samples from patients, the study aims to identify new biomarkers that could improve cancer diagnosis and guide more personalized therapies. The knowledge generated from this research may ultimately contribute to better diagnostic tools and more effective treatments for cancer patients in our community.
Soluble Matrisomics to Identify Druggable Targets for Stroma-Directed Cancer Therapy
Investigator
Xiaoyu Shi, PhD, Department of Developmental & Cell Biology, UC Irvine School of Biological Sciences
Aggressive cancers like pancreatic and breast cancer are difficult to treat because they are surrounded by a dense "shell" of structural proteins and signaling molecules that block drugs and help the tumor grow. This research project develops a new technology called GEM-ECM to map these surrounding proteins, specifically targeting the hidden signaling factors that traditional methods often discard. By identifying these accessible targets, this work will pave the way for new therapies that can bypass the tumor's defenses and lead to novel treatment and earlier, non-invasive diagnosis. Ultimately, this project aims to improve survival rates for patients with hard-to-treat solid tumors by turning the tumor's own environment into a roadmap for more effective treatments.
UHRF1 as a Novel Regulator of Proteasome Function and Tumor Cell Fitness
Investigator
Claudia Benavente, PhD, Department of Pharmaceutical Sciences, UC Irvine School of Pharmacy and Pharmaceutical Sciences
Cancer cells rely on efficient protein quality control to survive proteotoxic stress driven by oncogenic signaling and rapid proliferation. The ubiquitin-proteasome system, and specifically the 26S proteasome, is the primary pathway responsible for selective protein degradation; however, the molecular mechanisms that regulate proteasome function in solid tumors remain incompletely defined. UHRF1 is a multidomain protein frequently overexpressed in aggressive cancers and classically associated with DNA methylation and chromatin regulation. Emerging evidence indicates that UHRF1 may also associate with proteasome complexes through a ubiquitination-independent mechanism, suggesting a previously unrecognized role in proteostasis. This project will test the hypothesis that UHRF1 functions as a regulatory component of the proteasome that enhances proteasome assembly and/or activity, thereby promoting tumor cell fitness. Aim 1 will define the molecular interface between UHRF1 and proteasome complexes using domain-mapping and biochemical approaches. Aim 2 will determine whether UHRF1 regulates proteasome assembly and catalytic function, including ubiquit independent substrate degradation. Aim 3 will evaluate the contribution of UHRF1-dependent proteasome regulation to tumor cell fitness and proteostasis under stress conditions. These studies will establish a mechanistic framework linking UHRF1 to protein degradation and define a novel regulatory axis in cancer biology. The findings are expected to reveal new insights into how tumor cells modulate proteasome function and may identify vulnerabilities that can be exploited therapeutically in aggressive cancers.
TRACK 2: EARLY PHASE CLINICAL TRIALS
Circulating Tumor DNA (ctDNA) as a Biomarker for Total Neoadjuvant Therapy in Stage III Melanoma
Investigator
Poorva Vaidya, MD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
In Stage III melanoma, pre-operative immunotherapy confers a recurrence free survival benefit and yields a pathologic complete response rate close to 50%; however, it remains unknown how many cycles of treatment are optimal prior to surgery and if levels of circulating tumor DNA (ctDNA) inform duration of treatment. We aim to answer both questions in this clinical trial titled “Total Neoadjuvant Therapy for Melanoma.” Melanoma highly impacts the patient population treated at Chao Family Comprehensive Cancer center and further elucidating the role of pre-operative immunotherapy in its treatment will meet a large clinical need for UC Irvine’s catchment area.
Phase 1B Randomized Study of Gemcitabine (G) with or without Pitavastatin (P) in the maintenance treatment of unresectable pancreatic adenocarcinoma (uPDAC)
Investigator
Jennifer Valerin, MD, PhD, Division of Hematology/Oncology, Department of Medicine, UC Irvine School of Medicine
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related death in the United States and projected to be the second leading cause by 2030. Gemcitabine is the most commonly used chemotherapy PDAC. However, cells can become resistant to gemcitabine and pitavastatin, a medication to treat high cholesterol has been shown to prevent resistance. Here we plan a clinical trial to combine gemcitabine therapies and pitavastatin to improve cancer outcomes.
