Roy A Jensen

University of Kansas | KU · Department of Pathology and Laboratory Medicine

Inherited defects in the breast cancer susceptibility gene, BRCA1 are associated with an increased risk for hereditary breast, ovarian, and other cancers. BRCA1-associated basal like breast cancers (BLBCs) are high-grade ductal carcinomas that do not express ER, PR or HER2, but frequently overexpress epidermal growth factor receptor (EGFR/ErbB1/HER...

The role of BRCA1 in cellular metabolism is not well characterized and what we do understand has been mostly demonstrated in vitro. Our studies aim to fully characterize the role of BRCA1 in metabolic pathways in a whole-body system. In vivo studies using C57BL/6 wild-type and transgenic humanized BRCA1 mice demonstrate the effect of human BRCA1 on...

The Accelerate Cancer Education (ACE) summer research program at The University of Kansas Cancer Center (KUCC) is a six-week, cancer-focused, summer research experience for high school students from historically marginalized populations in the Kansas City metropolitan area. Cancer affects all populations and continues to be the second leading cause...

Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells (CSCs) contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. IRA...

The University of Kansas Cancer Center (KU Cancer Center) initiated an engagement program to leverage the lived experience of individuals and families with cancer. KU Cancer Center faculty, staff, and patient partners built an infrastructure to achieve a patient-designed, patient-led, and research-informed engagement program called Patient and Inve...

Purpose There is an increasing awareness of the importance of patient engagement in cancer research, but many basic and translational researchers have never been trained to do so. To address this unmet need, a 1-year patient engagement training program for researchers was developed. Methods Eleven researchers and eleven paired research advocates p...

TPS7078 Background: Fosciclopirox (CPX-POM) is a broad-spectrum anticancer agent being developed through a public-private partnership between CicloMed LLC and KU Cancer Center (KUCC). Following intravenous administration, fosciclopirox is rapidly and completely metabolized to its active metabolite ciclopirox (CPX). Given fosciclopirox is a prodrug...

Ovarian cancer (OvCa) is the leading cause of gynecologic cancer-related deaths, due in part to late-stage diagnoses. While the overall response rate to first line therapy is encouraging (~80%), the majority of women develop recurrent disease, characterized by resistance to standard chemotherapy. There is convincing evidence that cancer stem cells...

The capacity and diversity of the oncology leadership workforce has not kept pace with the emerging needs of our increasingly complex cancer centers and the spectrum of challenges our institutions face in reducing the cancer burden in diverse catchment areas. Recognizing the importance of a diverse workforce to reduce cancer inequities, the Associa...

Prostate cancer is the most common cancer among men. Currently, targeting the AR pathway, chemotherapy or immune-based therapies are major options but only provide a modest improvement in overall survival. RNA binding proteins have been shown to regulate AR expression in the progression of PCa. We and others have demonstrated that RNA binding prote...

Ovarian cancer (OvCa) is the leading cause of gynecologic cancer-related deaths. While the overall response rate to first line therapy is encouraging (~80%), the majority of women develop recurrent disease that is characterized by resistance to chemotherapy. It is believed that cancer stem cells (CSCs) may contribute, in part, to resistance and rec...

TPS7069 Background: Fosciclopirox (F) is a γ-secretase inhibitor being developed for the treatment of acute myeloid leukemia (AML). Following intravenous (IV) administration, F is rapidly and completely metabolized to its active metabolite, ciclopirox (CPX). CPX binds to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential f...

e16540 Background: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ̃40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usu...

6542 Background: Access to health care including clinical trials (CT) leading to paradigm-changing cancer treatments are critical for high quality cancer care and equity in society. In this report, we highlight methods in accruing to ETCTN wherein underrepresented rural, low-income, and racial minorities comprise >50% of enrollment. Methods: Univer...

Background Breast cancer is the most common malignancy in women, and is both pathologically and genetically heterogeneous, making early detection and treatment difficult. A subset of breast cancers express normal levels of REST (repressor element 1 silencing transcription factor) mRNA but lack functional REST protein. Loss of REST function is seen...

Breast cancer is the most common malignancy in women and is the second leading cause of cancer-related deaths. Breast cancer is both pathologically and genetically heterogeneous, making early detection and treatment difficult. A subset of breast cancers expresses normal levels of REST (Repressor Element 1 Silencing Transcription factor) mRNA but la...

Gene fusions are known to drive many human cancers. Therefore, the functional characterization of newly discovered fusions is critical to understanding the oncobiology of these tumors and to enable therapeutic development. NPM1–TYK2 is a novel fusion identified in CD30 + lymphoproliferative disorders, and here we present the functional evaluation o...

Background and Aims: Translational regulation involve the coordinated actions of RNA binding proteins (RBPs) and non-coding RNAs. For efficient translation, the mRNA needs to be circularized. While RNA binding proteins and translation factors have been shown to regulate the circularization, the role of lncRNAs in the process is not yet defined. Met...

Importance Screening for breast and colorectal cancer has resulted in reductions in mortality; however, questions remain regarding how these interventions are being diffused to all segments of the population. If an intervention is less amenable to diffusion, it could be associated with disparities in mortality rates, especially in rural vs urban ar...

Background More than 80% of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients harbor the (nucleophosmin) NPM1-ALK fusion gene t(2;5) chromosomal translocation. We evaluated the preclinical and clinical efficacy of ceritinib treatment of this aggressive lymphoma. Materials and methods We studied the effects of...

Honokiol (HNK) is a biphenolic compound that has been used in traditional medicine for treating various ailments, including cancers. In this study, we determined the effect of HNK on colon cancer cells in culture and in a colitis-associated cancer model. HNK treatment inhibited proliferation and colony formation while inducing apoptosis. In additio...

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (C...

Triple negative breast cancer (TNBC) is observed in ~15% of breast cancers and results in poor survival and increased distant metastases. Within the tumor are present a small portion of cancer stem cells that drive tumorigenesis and metastasis. In this study, we aimed to elucidate whether the two natural compounds, celastrol and triptolide, inhibit...

Background: Breast cancer is the most common malignancy in women, and is both pathologically and genetically heterogeneous, making early detection and treatment difficult. A subset of breast cancers express normal levels of REST (repressor element 1 silencing transcription factor) mRNA but lack functional REST protein. Loss of REST function is seen...

Anaplastic large cell lymphoma (ALCL) is an aggressive type of non-Hodgkin lymphoma. More than three-fourths of anaplastic lymphoma kinase (ALK)-positive ALCL cases express the nucleophosmin 1 (NPM1)-ALK fusion gene as a result of t(2;5) chromosomal translocation. The homodimerization of NPM1-ALK fusion protein mediates constitutive activation of t...

Purpose: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response(pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in TNBC. Aim of NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens....

Background: The oncology community faces unprecedented challenges in balancing a delay in cancer treatment against the risk for a potential COVID-19 infection and associated complications. An early retrospective analysis reported that cancer patients with COVID-19 infection have a much higher death rate than those infected but without a cancer diag...

Ciclopirox (CPX) is a FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in solid and hematologic malignancies. It's clinical utility as an anticancer agent, however, is limited by poor oral bioavailability, gastrointestinal toxicity, and poor water solubility. Fosciclopirox, the phosphoryloxymethyl ester of...

Breast cancer, the most common malignancy in women, is very difficult to detect and treat due to its heterogeneity. An important subset of breast cancers, Luminal or ER/PR positive tumors, lack REST (repressor element 1 silencing transcription factor) protein but not its mRNA. REST is a tumor suppressor and is known to play a role in regulating neu...

RNA binding proteins play a significant role in regulating gene expression, and dysregulation in their expression may skew cells to various pathophysiological conditions. In previous studies, we demonstrated that RNA binding protein RBM3 acts as a protooncogene, with its expression. Increasing in a stage dependent manner in colon cancers. To get a...

Background The SARS–CoV-2 pandemic has assaulted all aspects of daily life. Medical professionals in oncology face additional challenges with balancing prompt cancer diagnosis and urgent treatment against potential COVID-19 exposure risk in these high-risk patients. We designed this prospective freewill study to offer testing for SAR2-CoV-2 viral R...

518 Background: Fosciclopirox (CPX-POM) is being developed for the treatment of non-muscle invasive and muscle invasive bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox (CPX), to the entire urinary tract following systemic administration. In a chemical carcinogen mouse model of bladder cancer, CPX-POM treatment resulte...

TPS604 Background: Fosciclopirox (Ciclopirox Prodrug, CPX-POM) is being developed for the treatment of non-muscle invasive and muscle invasive (MIBC) bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox (CPX), to the entire urinary tract following systemic administration. In a validated, chemical carcinogen mouse model of...

Cancer stem cells (CSCs) have the ability to self-renew and induce drug resistance and recurrence in colorectal cancer (CRC). As current chemotherapy doesn’t eliminate CSCs completely, there is a need to identify novel agents to target them. We investigated the effects of cucurbitacin B (C-B) or I (C-I), a natural compound that exists in edible pla...

To the Editor In their recently published Research Letter,¹ Carr and Welch are right to raise concerns about the influence of industry funding on clinical research. However, their article implies that all such relationships are inherently problematic, despite the lack of details about the services provided. It is also not apparent whether any cance...

An increasingly diversified demographic landscape in rural and urban America warrants the attention of The University of Kansas Cancer Center (KU Cancer Center) researchers, clinicians, outreach staff and administrators as the institution assesses ways to reach its expansive, bi-state catchment area. Within the counties of the KU Cancer Center catc...

To fully support their role in translational and personalized medicine, biorepositories and biobanks must continue to advance the annotation of their biospecimens with robust clinical and laboratory data. Translational research and personalized medicine require well-documented and up-to-date information, but the infrastructure used to support biore...

Anaplastic large cell lymphoma (ALCL) is an aggressive type of non-Hodgkin's lymphoma (NHL) comprising 2-8% of adult and 10-20% of pediatric and adolescent NHL. More than three-fourths of anaplastic lymphoma kinase (ALK)-positive ALCL express (nucleophosmin1) NPM1-ALK fusion gene as a result of t(2;5) chromosomal translocation. The self-dimerizatio...

IRAK1: a novel TOLLway to target chemoresistant ovarian cancer Standing, David1, Dandawate, Prasad1, Chaudhary, Suman2, Pritchard, Michele T.3, Subramaniam, Dharmalingam1, Petersen, Shariska4, Khabele, Dineo4, Roby, Katherine5, Jensen, Roy A.6, Weir, Scott J.1,3, Anant, Shrikant1 1Departments of Cancer Biology, University of Kansas Medical Center 2...

Background & aims: Prolactin (PRL) signaling is upregulated in hormone-responsive cancers. The PRL receptor (PRLR) is class I cytokine receptor that signals via the JAK-STAT and MAPK pathways to regulate cell proliferation, migration, stem-cell features, and apoptosis. Patients with pancreatic ductal adenocarcinoma (PDAC) have high plasma levels o...

Background & aims: The histone lysine demethylase 3A (KDM3A) demethylates H3K9me1 and H3K9Me2 to increase gene transcription and is upregulated in tumors, including pancreatic tumors. We investigated its activities in pancreatic cancer cell lines and its regulation of the gene encoding doublecortin calmodulin-like kinase 1 (DCLK1), a marker of can...

p97 is an ATPase that works in concert with histone deacetylase 6 (HDAC6), to facilitate the degradation of misfolded proteins by autophagosomes. p97 has also been implicated in DNA repair and maintaining genomic stability. In this study, we determined the effect of combined inhibition of p97 and HDAC6 activities in mantle cell lymphoma (MCL) cells...

Pancreatic ductal adenocarcinoma (PDAC) is the major leading cause of cancer related human death in USA. There is no possible treatment or target available in PDAC. It was proposed that the cancer stem cells (CSCs) can regulates malignancy in PDAC. DCLK1 is one of the quiescent cancer stem cell marker in PDAC that can regulate tumor progression. Id...

Electronic health records (EHR) represent a rich resource for conducting observational studies, supporting clinical trials, and more. However, much of the data contains unstructured text, presenting an obstacle to automated extraction. Natural language processing (NLP) can structure and learn from text, but NLP algorithms were not designed for the...

Pharmacokinetic studies in rats and dogs were performed to characterize the in vivo performance of a novel prodrug, fosciclopirox. Ciclopirox olamine (CPX-O) is a marketed topical antifungal agent with demonstrated in vitro and in vivo preclinical anticancer activity in several solid tumor and hematologic malignancies. The oral route of administrat...

516 Background: Addition of neoadjuvant carboplatin (Cb) to paclitaxel (T) followed by doxorubicin + cyclophosphamide (AC) improves pathologic complete response (pCR) rate compared to T/AC in TNBC. An anthracycline-free regimen of Cb plus docetaxel (D) also yields high pCR rates in TNBC, and patients achieving pCR with this regimen demonstrate exce...

e14705 Background: Ciclopirox Prodrug (CPX-POM) is a novel anticancer agent currently being evaluated in patients with advanced solid tumors participating in a First-in-Human, Phase 1 safety, dose tolerance, pharmacokinetics (PK) and pharmacodynamics trial at four US sites. In vitro and in vivo preclinical proof of principle was established in high...

We previously reported that ionizing radiation (IR) mediates cell death through the induction of CUGBP elav‐like family member 2 (CELF2), a tumor suppressor. CELF2 is an RNA binding protein that modulates mRNA stability and translation. Since IR induces autophagy, we hypothesized that CELF2 regulates autophagy‐mediated colorectal cancer (CRC) cell...

BRCA1 (breast cancer 1, early onset), a well-known breast cancer susceptibility gene, is a highly alternatively spliced gene. BRCA1 alternative splicing may serve as an alternative regulatory mechanism for the inactivation of the BRCA1 gene in both hereditary and sporadic breast cancers, and other BRCA1-associated cancers. The alternative transcrip...

Anaplastic large cell lymphoma (ALCL) represents a rare and aggressive subtype of CD30-positive peripheral T-Cell lymphoma which accounts for 5-10% of non-Hodgkin lymphomas in adults and 10-30% in children. More than 80% of ALK-positive ALCLs hallmarked by fusion gene NPM1-ALK generated by t(2;5) chromosomal translocation. The fusion kinase NPM1-AL...

Metastasis is a major cause of cancer-related deaths. A dearth of preclinical models that recapitulate the metastatic microenvironment has impeded the development of therapeutic agents that are effective against metastatic disease. Because the majority of solid tumors metastasize to the lung, we developed a multicellular lung organoid that mimics t...

Many inbred strains of mice develop spontaneous tumors as they age. Recent awareness of the impacts of mitochondrial DNA (mtDNA) on cancer and aging has inspired developing a mitochondrial-nuclear exchange (MNX) mouse model in which nuclear DNA is paired with mitochondrial genomes from other strains of mouse. MNX mice exhibit mtDNA influences on tu...

Epstein–Barr virus (EBV) is directly implicated in several B-cell lymphoid malignancies. EBV-associated lymphomas are characterized by prominent activation of the NF-κB pathway and targeting this pathway establishes a rationale for a therapeutic approach. The ubiquitin/proteasome signaling plays an essential role in the regulation of the NF-κB path...

Purpose: Prognostic value of pCR and extent of pathological response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in TNBC is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathological response in patients treated with carboplatin (Cb) plus docetaxel (D) NA...

Metastatic colorectal cancer is a major cause of cancer-related deaths. Most patients with metastatic disease fail to respond to current chemotherapeutic agents. Current, traditional culture model is not appropriate to study the metastatic disease in in vitro condition. Hence, there is an ominous need for developing new therapeutic and preventive a...

Ciclopirox (CPX) is contained in a number of FDA-approved topical antifungal drug products as the free acid and olamine salt. CPX possesses anticancer activity in a number of in vitro and in vivo preclinical models. Its clinical utility is limited as an oral anticancer agent, however. The oral bioavailability of CPX is quite low due to extensive fi...

Pancreatic cancer (PCa) is deadly cancer with an abysmal five‐year survival rate of < 6%. PCa has a bad prognosis and is associated with resistance to standard of care chemotherapeutic gemcitabine and high recurrence rate after surgery. Unfortunately, gemcitabine remains the drug of choice for metastatic pancreatic adenocarcinoma, with minor improv...

We identified SMYD2, a SMYD (SET and MYND domain) family protein with lysine methyltransferase activity, as a novel breast cancer oncogene. SMYD2 was expressed at significantly higher levels in breast cancer cell lines and in breast tumor tissues. Silencing of SMYD2 by RNAi in triple-negative breast cancer (TNBC) cell lines or inhibition of SMYD2 w...

Background: The impact of age at diagnosis on clinical presentation and treatment delivery for triple negative breast cancer (TNBC) is unclear. Utilizing data from a prospective registry, the aim of this study was to further elucidate the age-dependent correlation between TNBC clinical-pathological features, and the implications of age-bias on trea...

Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with N...

Using a novel mouse model, a mitochondrial nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA and either FVB/NJ, C57BL/6J or BALB/cJ mtDN...

Background: Colon cancer is the second leading cause of death in the United States. Previously, we have reported that the identification of a novel compound Marmelin from Aegle marmelos and potent anti-colon cancer activity. We have developed novel Marmelin analogue THB from this structure showed potent anti-cancer activity and its inhibitory const...

Background: Triple-negative breast cancers (TNBCs) are highly associated with an aggressive clinical course, resistance to chemotherapy, and poor prognosis compared to other breast cancer subtypes. However, breast cancers arising in BRCA1 mutation carriers appear to be particularly sensitive to platinum-based chemotherapy agents. The tumor suppress...

Introduction: Pathological complete response (pCR) in unselected triple negative breast cancer (TNBC) is associated with excellent long-term survival. However, controversy remains as to whether pCR in mutation associated ([+]) TNBC is predictive of improved long-term outcome. A recent study suggests that pCR was not a surrogate for outcomes in 1 as...

The presentation and treatment of ductal carcinoma in situ (DCIS) has changed substantially over the years. While previously an incidental pathologic finding in more advanced, palpable tumors, the institution of screening mammography has repositioned this disease entity as one largely diagnosed as a non-palpable lesion, often prior to any invasive...

Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and dru...

Background: Pancreatic cancer (PCa) remains a leading cause of death in the United States. Cancer stem cells (CSC) are responsible for tumor behavior, and therapeutic resistance. Quinomycin (Qui) is an orally administered quinoxaline antibiotic that bifunctionally intercalates with double stranded DNA. As a first step for repurposing this drug, we...

Background: Pancreatic cancer (PCa) is a major cause of cancer related mortality in United States with < 6% survival rate. It is an aggressive and devastating disease, which is characterized by poor prognosis, invasiveness, rapid progression, profound resistance to drug treatment and recurrance after surgery. Presently, single agent based chemother...

Background: Breast cancer is the second leading cause of death for woman. Within breast cancer, those classified as Triple Negative Breast Cancer (TNBC) exhibit dismal survival rates due to their propensity to develop distant metastases. Heat shock protein 90 (Hsp90) is a molecular chaperone that aids in the folding and maturation of various protei...

Background: Despite therapeutic advances, colon cancer remains the second leading cause of death in the United States. Previously, we have reported that the identification of a novel compound, HDNC or Marmelin from Aegle marmelos with potent anti-colon cancer activity. We have now developed a novel marmelin analogue THB and made it water soluble TH...

Background: Triple Negative Breast Cancer (TNBC) exhibit dismal survival rates due to their propensity to develop distant metastases. Heat shock protein 90 (Hsp90) is a molecular chaperone that aids in the folding and maturation of various proteins involved in breast cancer progression and resistance to therapy. Many studies have also suggested tha...

Background: Triple-negative breast cancers (TNBCs) are highly associated with an aggressive clinical course and poor prognosis, largely due to resistance to chemotherapy. Platinum-based therapies act by causing DNA damage, which in the absence of a functional DNA repair system, leads to cancer cell death. BRCA1, a well-studied tumor suppressor, is...

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxe...

Background: Participation in cancer clinical trials has been shown to increase overall survival with minimal increase in cost, but enrollment in adult cancer clinical trials remains low. One factor limiting enrollment is lack of insurance coverage, but this barrier should be reduced under the 2010 Patient Protection and Affordable Care Act (ACA), w...

Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notc...

Modern cancer therapy/care involves the integration of basic, clinical, and population-based research professionals using state-of-the-art science to achieve the best possible patient outcomes. A well-integrated team of basic, clinical, and population science professionals and educators working with a fully engaged group of creative junior investig...

Background: Pancreatic cancer (PCa) remains a leading cause of death in the United States. Cancer stem cells (CSC) are responsible for tumor behavior, and therapeutic resistance. Quinomycin (Qui) is an orally administered quinoxaline antibiotic that bifunctionally intercalates with double stranded DNA. As a first step for repurposing this drug, we...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background: Despite advances in early detection, colon cancer remains the second leading cause of death in the United States. We are focused on developing dietary prevention strategies. HNK (HNK) is a biphenolic compound that is used in the traditional Chinese Medicin...

Introduction: Growing evidence demonstrates activity of neoadjuvant carboplatin in triple negative breast cancer (TNBC). Underlying germline and somatic Homologous Recombination (HR) repair deficiency may predict response to DNA damaging agents like platinum compounds in TNBC. Certain DNA repair machinery genes (Fanconi Anemia gene) are also involv...

Heat shock factor 1 (HSF1) is a stress-inducible transcription factor and has been described as a multi-faceted modulator of tumorigenesis. Heat shock, accumulation of misfolded proteins, or malignant transformation promotes the activation and nuclear translocation of HSF1, where it binds to the promoters of heat shock proteins and an array of nonh...