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Administrative Core
CORE A SUMMARY/DESCRIPTION Core A is critical to the operation of this program project, and has three major aims. In Aim 1, core A will initiate and organize regular communication...
Replication Stress Sensing and Signaling Defects in SCLC
PROJECT SUMMARY The underlying mechanisms that account for initial sensitivity to of SCLC to chemotherapy followed by profound therapeutic resistance are just beginning to be eluci...
Roles of TIMELESS in oncogene-induced senescence and oncogenic transformation
PROJECT SUMMARY Oncogenic stimuli in early cancerous lesions, such as driven by RAS mutations, triggers oncogene-induced senescence (OIS), which acts as a barrier to prevent malign...
From Perceptions to Behaviors: A Comprehensive Approach to Examine the Impact of Public Health Communication Messaging about the Continuum of Risk for Tobacco Products
PROJECT SUMMARY Effective communication strategies are urgently needed to convey the relative risks of tobacco products accurately among adults who currently use combustible tobacc...
Development and application of whole-body patient-specific computational mesh phantoms for organ dosimetry and second primary cancer risk quantification following external beam radiotherapy
PROJECT SUMMARY Approximately half of all cancer patients in the United States are treated with external beam radiotherapy (RT), with approximately 40% of all curative treatment be...
Improving engineered TCR-T cell therapy for solid tumors by targeting Tcf1+ stem-like reservoirs in tumor-draining lymph nodes
PROJECT SUMMARY Adoptive transfer of engineered T cells targeting tumor antigens is ineffective against most solid tumors, due in-part to poor persistence and the rapid onset of dy...
Enzyme-Mediated Depletion of Extracellular Adenosine and 5'methylthioadenosine as a Novel Anti-Cancer Therapeutic
PROJECT SUMMARY In recent years, adenosine has been identified as an important therapeutic target due to its observed immunosuppressive effects in the tumor microenvironment. By ag...
Defining the role of NUDT5 in ovarian cancer
Ovarian cancer patients are burdened with a lack of effective therapeutic options resulting in a low survival rate due to chemotherapy resistance, recurrence, and metastasis. The o...
Mechanisms of Replication Stress Tolerance in SCLC
PROJECT 2 SUMMARY Exacerbating replication stress is a powerful means to kill cancer cells through mitotic catastrophe due to intolerable levels of DNA replication-associated lesio...
Repair Mechanisms of Replication fork Lesions in SCLC
PROJECT SUMMARY This project will investigate the specific mechanisms of DNA lesions that are generated in SCLC during treatment and lead to response or resistance to therapy. This...
Impact of recurrent genetic alterations on SCLC subtypes and therapeutic response
Project Summary Small cell lung cancer (SCLC) is a highly aggressive malignancy with high heterogeneity and few available treatment options. SCLC cells are of highly plastic enabli...
SCLC Model Generation and Therapeutic Analysis
Project Summary The laboratory mouse plays a central role in the preclinical development of new therapeutic strategies and through the application of transgenic technology has prov...
Advanced Imaging and Computational Approaches
The Advanced Microscopy and Computational Approaches Core (Core C) will provide advanced imaging and computational approaches to support this Program Project in elucidating the mol...
An Acceptance and Commitment Therapy-Based Psychosocial Intervention to Alleviate Distress and Promote Adaptive Coping Skills in Patients with Malignant Primary Central Nervous System Tumors
Project Summary/Abstract Malignant primary central nervous system (CNS) tumors are incurable tumors characterized by high symptom burden and poor survival. In addition to the sympt...
Dissecting the cooperation of FOXR2 and ETS transcription factors in FOXR2-expressing diffuse midline gliomas
PROJECT SUMMARY Diffuse midline gliomas (DMGs) are devastating childhood brain tumors for which there are no effective therapies. While histone mutations are thought to be a critic...
Stroma-penetrating nanomedicine to improve treatment for pancreatic cancer
PROJECT SUMMARY Annually, pancreatic cancer (PC) has a global incidence of more than 495,000 cases and a mortality rate of almost 460,000 cases. Most of these patients (~80%) recei...
Phase 1 First in Human Trial to Assess Safety and Tolerability of the Novel ACK1 Inhibitor (R)-9b in Patients with Prostate Cancer
Abstract Prostate cancer (PC) is one of the leading cause of cancer deaths among American men. Advanced PC patients often receive androgen deprivation therapy, but, the recalcitran...
Rewired Metabolism and Immunosuppression in MYCN-driven Neuroblastoma
PROJECT SUMMARY Amplification of the oncogene MYCN drives high-risk progressive disease, resistance to therapy, and a poor overall survival rate below 45% for high-risk neuroblasto...
Cell Competition in Development and Homeostasis
A process of cell competition can remove cells that differ genetically from neighboring cells in the same tissues. Cell competition helps to eliminate sporadic aneuploid cells that...
Targeting mitochondrial calcium to eradicate leukemia-initiating cells
SUMMARY The goal of this project is to develop strategies for the eradication of leukemia-initiating cells (LICs) in AML patients who have received initial therapy with venetoclax...