Cell and Developmental Biology Commons^™

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

Therapeutic Vulnerabilities Of Venetoclax Resistant Chronic Lymphocytic Leukemia And Novel Treatment Strategies Targeting Bcl2/Bcl-Xl, Daisy Y. Diaz-Rohena

Dissertations and Theses (Open Access)

Despite major advancements in the management of chronic lymphocytic leukemia (CLL), drug resistance remains a major challenge. CLL resistant to venetoclax (VEN) have limited available therapeutic options, especially when the leukemic cells have dysfunctional p53 and have relapsed on Bruton’s tyrosine kinase inhibitors (BTKi). The broad hypothesis of this thesis is that VEN-relapsed CLL exhibits altered dependence on BCL2 family members, which can be exploited for therapeutic benefit. I profiled 28 CLL samples collected from 15 patients either at baseline or at relapse following VEN treatment, which was administered in combination with a BTKi or sequentially as monotherapy after a …

Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer related deaths with nearly a quarter of patients presenting with metastatic disease at the time of their diagnosis. Therapeutic management of metastatic CRC continues to be a major challenge due to therapy resistance and disease heterogeneity. Due to its central role in tumorigenesis, CRC is commonly treated with MAPK pathway inhibitors (MAPKi). However, clinical trials repeatedly demonstrates that durability of benefit is short-lived in many patients. While genomic mechanisms of acquired resistance have been described, they explain a minority of patients, and further research is needed to determine the underlying …

Identification Of Mitochondrial Defects And Metabolic Consequences In Lynch Syndrome-Related Endometrial Cancer, Mikayla Bowen

Dissertations and Theses (Open Access)

Lynch syndrome (LS), defined by mutations in DNA mismatch repair genes including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Mismatch repair deficiency (MMRd) causes hypermutability, which is assumed to be the main driver of LS-related EC development. However, incomplete penetrance of EC development in women with LS suggests that other modulators are at play. The broad hypothesis of this dissertation is that MMRd causes consequences beyond hypermutability to impact LS-related EC development. Recent studies utilizing our lab’s Msh2-deficient mouse model for LS-EC revealed mitochondrial dysfunction in EC pathogenesis. This new insight led to the …

Developing Novel Therapies Targeting The Tumor Microenvironment Of Aggressive Breast Cancer, Lan T H Phi

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive breast cancer subtypes. The tumor microenvironment (TME) is critical in driving these aggressive breast cancers' clinical phenotype and aggressiveness. Therefore, we explored novel actionable targets and complementary therapies targeting the TME to improve the outcomes of patients with these cancers.

In this thesis, we identified AXL as a potential therapeutic target in IBC due to its role in generating an immunosuppressive TME. Indeed, inhibiting the AXL pathway suppresses IBC tumor growth and reduces M2 macrophage populations in various mouse models. Mechanistically, AXL facilitates the polarization of M2 …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Relationship Between Processing Body Formation, Epithelial-To-Mesenchymal Transition, And Invasion In Lung Adenocarcinoma, Amanda Warner

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths in the United States, largely due to its ability to metastasize. Epithelial-to-mesenchymal transition (EMT) is a process that enhances the ability of cells to lose their cell-cell contacts, invade, and enter the blood stream which are essential during metastasis. Many transcriptional gene programs are altered during EMT such as activation of mesenchymal transcription factors, like ZEB1, and enhanced response to the TGFβ1 cytokine. In oncogenic contexts, TGFβ1 enhances the formation of processing-bodies (P-bodies) where P-body proteins are required for invasion in multiple cancerous cell lines. P-bodies are a type of ribonucleoprotein …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

Harnessing The Immunomodulatory Potential Of Radiofrequency Ablation To Improve Therapeutic Outcomes In Pancreatic Ductal Adenocarcinoma, Bhumi Maniyar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) continues to rank among the most lethal cancers with poor prognosis. PDAC is characterized by a thick desmoplastic stroma, severe immunological suppression, and resistance tostandard treatments. The need for innovative therapeutic approaches is highlighted by the tumor microenvironment's (TME) critical role in promoting disease development and reducing the effectiveness oftreatment. A promising locoregional treatment that can induce tumor necrosis and modify the TME is endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA). However, there is still minimal understanding around its wider impact on stromal remodeling and immunological activation. This study investigates the immunomodulatory effects of RFA combined with neoadjuvant …

Role Of Mir-4732-3p In Breast Cancer Brain Metastasis And Brain Metastatic Tumor Microenvironment, Munazza Samar Khan

Dissertations and Theses (Open Access)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. MiR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …

Wired For Degradation: How Post-Translational Control Of Inducible Camp Early Repressor Protein Influences Melanoma Fate, Melissa Rose Spigelman

Theses, Dissertations and Culminating Projects

Melanoma is a highly aggressive form of skin cancer frequently driven by mutations in the BRAF gene, particularly the BRAFⱽ⁶⁰⁰ᴱ variant, which leads to sustained activation of the MAPK signaling cascade. Recent studies implicate the cyclic AMP (cAMP) signaling axis in melanoma progression and therapeutic resistance, highlighting the role of the Inducible cAMP Early Repressor (ICER), a transcriptional antagonist of CREB and CREM. ICER is downregulated during melanomagenesis and subject to post-translational regulation via phosphorylation and ubiquitin-mediated degradation. To investigate ICER’s functional relevance in vivo, e utilized a zebrafish melanoma model harboring brafⱽ⁶⁰⁰ᴱ, tp53−/−, and mitf−/−mutations, in which mitf expression …

The Development Of Magmas Inhibition As A Potential Therapeutic Target In Temozolomide Resistant Glioma, Jennifer Duyen Tran

Electronic Theses, Projects, and Dissertations

Glioblastoma (GBM) is a highly aggressive brain tumor that remains a significant challenge in neuro-oncology today. Approximately 90% of GBM patients experience tumor recurrence within one to two years of diagnosis. Therefore, due to its high resistance to conventional therapies, new treatment strategies are urgently needed. The current standard of care for GBM is the chemotherapeutic Temozolomide (TMZ). TMZ is an oral alkylating agent, it functions by delivering a methyl group to purine bases. The development of resistance to TMZ is partially regulated by the DNA repair enzyme O6- methylguanine-DNA methyltransferase (MGMT). Despite the potential shown by MGMT promoter methylation …

Mcf-7 Dense Breast Cancer Cells Modulate Stress Through Senescence, Lara Donadio, Moses Alfonso, Josiah Philip, Tyler Zatarain

Molloy Multidisciplinary Undergraduate Research Conference

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, with dense breast tissue being recognized as a significant risk factor for its development. This dense breast tissue, characterized by a higher concentration of mammary glandular tissue, represents additional sites for tumor development. The following study explores how the MCF-7 immortal cell line, representing dense breast cancer, modulates stress responses through cellular senescence. Cellular senescence is a defense mechanism that halts the cell cycle and acts as a tumor suppression mechanism, preventing out-of-control cell proliferation triggered by cytological stress. To simulate these stress conditions, we applied two agents: …

Enhancing Skin Cancer Literacy Amongst Young Adults: A Digital Design, Katherine Stoll

Honors Projects

The skin plays a vital role in protection, regulation, and homeostasis of the human body. Skin cancer, despite being mostly preventable, is one of the most common cancers. Young adults, ages 18 to 25, are vulnerable targets due to risky behaviors and misinformation regarding skin cancer. This project was designed by using digital media and website design to enhance skin cancer health literacy among young adults. Using a systematic literature review and research methods, an interactive website was designed to improve skin cancer health literacy and eliminate common misconceptions. The topics addressed throughout the website were the biological factors of …

Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh

Computer Science ETDs

Advancing personalized medicine depends on effectively integrating and interpreting the vast, heterogeneous landscape of biological data, from genomic sequences and transcriptomics to the insights embedded in scientific literature. Current machine learning models often focus on single data modalities, limiting their capacity to capture the multifaceted nature of biological systems. We address this gap by developing three attention-based machine-learning models integrating diverse data modalities. Firstly, DeepVul is a multi-task model that leverages cancer transcriptome data to predict genes critical for cancer survival and their corresponding drugs. Subsequently, LitGene refines gene representations by integrating textual information from the scientific literature. Finally, Protein2Text …

Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh

Medical Student Research Symposium

African American (AA) women have lower adherence to breast cancer screening guidelines, which may contribute to delayed diagnoses and reduced survival rates. These disparities are often influenced by limited access to quality healthcare and persistent inequities faced within Michigan. With Detroit's population being 77% AA, examining studies focused on the experiences of Black women within urban healthcare networks is essential to understanding the connections between demographic, socioeconomic factors, and breast cancer outcomes. To assess these studies, a literature search was conducted using Ovid Medline yielding 24 associated articles.

Mammogram rates among AA women in Detroit remain low, reflecting a complex …

Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo

Medical Student Research Symposium

Endometrial cancer is rising in incidence in the United States, notably among premenopausal women. This increase and the trend of delayed childbearing warrant the need for further advancement in fertility-sparing treatment for endometrial cancer. A gene left widely unexplored in its possible clinical utility as a target for fertility-sparing treatment is KMT2D, a lysine-specific methyltransferase and tumor suppressor. Preliminary gene set enrichment analysis on a 12Z endometriotic epithelial cell line identified TIMP3 as a gene that is possibly regulated by KMT2D expression. TIMP3 encodes an irreversible inhibitor of matrix metalloproteinases (MMPs), a well-recognized class of proteins as contributing to the …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

The Present And Future Of Robotic Surgery In Breast Cancer And Breast Reconstruction, Brett Allen, Alexis Knutson, Noama Iftekhar, Casey Giles, Jarrell Patterson, Joshua Macdavid, Richard Baynosa

Department of Plastic Surgery Faculty Research

Background: Breast cancer is the second most common cancer in women with an improving mortality rate and a growing need for reconstruction following oncologic resection. Advancements in robotic surgery and minimally invasive techniques have offered refinement to traditional open techniques of flap harvest for reconstruction, particularly regarding improved donor site morbidity. Methods: The literature review was based on a PubMed database search using the keyword “Robotic breast reconstruction” in conjunction with the Boolean operators “Flap”, “Latissimus”, and “DIEP” to specify the search. In total, 106 results were generated, which were then manually reviewed and condensed for a comprehensive stance on …

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

5-Hydroxymethylcytosine Sequencing Of Plasma Cell-Free Dna Identifies Epigenomic Features In Prostate Cancer Patients Receiving Androgen Deprivation Therapies, Qianxia Li, Chiang-Ching Huang, Shane Huang, Yijun Tian, Jinyong Huang, Amirreza Bitaraf, Xiaowei Dong, Marja T. Nevalainen, Manishkumar Patel, Jodie Wong, Jingsong Zhang, Brandon J Manley, Jong Y. Park, Manish Kohli, Elizabeth M. Gore, Deepak Kilari, Liang Wang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: We evaluated whether 5hmC signatures in cell-free DNA (cfDNA) are associated with treatment failure to androgen-deprivation therapies (ADT) among men with hormone-naive prostate cancer.

METHODS: We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at 3 time points including baseline (before initiating ADT, n = 55); 3 months (after initiating ADT, n = 55); and disease progression (n = 15) within 24 months or 24 months if no progression was detected (n = 14). We used selective chemical labeling sequencing to quantify 5hmC abundance across the genome and Kaplan-Meier analysis to assess …

Uncovering The Mechanisms Of Glioblastoma Relapse Prevention With Niclosamide And Camptothecin Treatment, Xiaoqian Fang, Araely Ruiz, Eunseo Yang, Brianna Morin, Kimberly Herrera-Toscano, Megan Szobody, Josue Fonseca, John-Beloved Osho, Raquel Lara

Research Symposium

Background: Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. In our previous studies, we demonstrated that niclosamide and camptothecin (CPT) synergistically suppressed the proliferation in human glioblastoma U87 MG cells. Recently, we observed that U87 MG cells failed to resume growth after the combined treatment was removed, a phenomenon not seen with either agent alone. We aimed to explore the sustained anti-tumor effects of niclosamide and CPT in GBM.

Methods: Human glioblastoma U87 MG cells were treated with 5 mM niclosamide, 5 mM …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …