Oncology Commons^™

Application Of Geographic Information Systems (Gis) In The Study Of Prostate Cancer Disparities: A Systematic Review, Christiane J. El Khoury

Department of Medical Oncology Faculty Papers

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature, and propose alternative approaches. Methods: This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through …

Neuroendocrine Gene Subsets Are Uniquely Dysregulated In Prostate Adenocarcinoma, Nicole M. Naranjo, Anne Kennedy, Anna Testa, Cecilia E. Verrillo, Adrian D. Altieri, Rhonda Kean, D. Craig Hooper, Jindan Yu, Jonathan Zhao, Oliver Abinader, Maxwell W. Pickles, Adam Hawkins, William Kevin Kelly, Ramkrishna Mitra, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP …

Parp-Ish: Gaps In Molecular Understanding And Clinical Trials Targeting Parp Exacerbate Racial Disparities In Prostate Cancer, Moriah L. Cunningham, Matthew J. Schiewer

Department of Urology Faculty Papers

PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair (HRR) defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer (PCa), and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in PCa, where African American (AA) males are twice as likely to develop and die from the …

Intensity Modulated Radiation Therapy With Stereotactic Body Radiation Therapy Boost For Unfavorable Prostate Cancer: Five-Year Outcomes, Michael Carrasquilla, Tamir Sholklapper, Abigail Pepin, Nicole Hodgins, Siyuan Lei, Abdul Rashid, Malika Danner, Alan Zwart, Grecia Bolanos, Marilyn Ayoob, Thomas Yung, Nima Aghdam, Brian Collins, Simeng Suy, Deepak Kumar, Ryan Hankins, Keith Kowalczyk, Nancy Dawson, Sean Collins

Einstein Health Papers

PURPOSE: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.

MATERIALS AND METHODS: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided …

Racial/Ethnic Disparities In Prostate Cancer 5-Year Survival: The Role Of Health-Care Access And Disease Severity, Christiane J. El Khoury, Sean A.P. Clouston

Department of Medical Oncology Faculty Papers

Introduction: Prostate cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location, as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various USA counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods: The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan–Meier method was performed for five racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the …

The Role Of Salvage Radical Prostatectomy In Patients With Radiation-Resistant Prostate Cancer, Jake Drobner, Alain Kaldany, Mihir S. Shah, Saum Ghodoussipour

Department of Urology Faculty Papers

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective …

Bispecific Psma Antibodies And Car-T In Metastatic Castration-Resistant Prostate Cancer., Kevin K Zarrabi, Vivek Narayan, Patrick Mille, Matthew R Zibelman, Benjamin Miron, Babar Bashir, William Kevin Kelly

Department of Medical Oncology Faculty Papers

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in men in the United States. The treatment paradigm for prostate cancer has evolved with the emergence of a variety of novel therapies which have improved survival; however, treatment-related toxicities are abundant and durable responses remain rare. Immune checkpoint inhibitors have shown modest activity in a small subset of patients with prostate cancer and have not had an impact on most men with advanced disease. The discovery of prostate-specific membrane antigen (PSMA) and the understanding of its specificity to prostate cancer has identified …

Dynamic Role Of Exosome Micrornas In Cancer Cell Signaling And Their Emerging Role As Noninvasive Biomarkers, Jaya Aseervatham

Department of Neurology Faculty Papers

Exosomes are extracellular vesicles that originate from endosomes and are released by all cells irrespective of their origin or type. They play an important role in cell communication and can act in an autocrine, endocrine, or paracrine fashion. They are 40–150 nm in diameter and have a similar composition to the cell of origin. An exosome released by a particular cell is unique since it carries information about the state of the cell in pathological conditions such as cancer. miRNAs carried by cancer-derived exosomes play a multifaceted role by taking part in cell proliferation, invasion, metastasis, epithelial–mesenchymal transition, angiogenesis, apoptosis, …

Review Of Cardiovascular Risk Of Androgen Deprivation Therapy And The Influence Of Race In Men With Prostate Cancer, James Fradin, Felix J. Kim, Grace Lu-Yao, Eugene Storozynsky, William K. Kelly

Department of Medical Oncology Faculty Papers

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen …

Bispecific T-Cell Engagers Therapies In Solid Tumors: Focusing On Prostate Cancer, Diana C Simão, Kevin K Zarrabi, José L Mendes, Ricardo Luz, Jorge A Garcia, William Kevin Kelly, Pedro C Barata

Department of Medical Oncology Faculty Papers

Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors' immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. …

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …

Racial Disparities In Diabetes Mellitus Prevalence In Prostate Cancer Patients On Androgen Deprivation Therapy, Sameh Gomaa, William Kelly, Do, Grace Lu-Yao, Phd, Edith Mitchell, Md, Tingting Zhan, Phd, Kuang-Yi Wen, Phd

Department of Medical Oncology Posters

Intro/Background

• Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostate cancer.
• ADT has show to prolong survival.
• The use of ADT is associated with many side effects, most notably an increase in diabetes incidence for patients on ADT.
• African American men have higher prevalence and mortality rates from prostate cancer than White men.
• It is unclear how prostate cancer treatment such as ADT affects these disparities.
• This study examines racial differences in the prevalence of diabetes mellitus in prostate cancer patients based on their ADT status in the US.

Bone Health Management In The Continuum Of Prostate Cancer Disease, Ettickan Boopathi, Ruth Birbe, Sunday A. Shoyele, Robert B. Den, Thangavel Chellappagounder

Department of Medicine Faculty Papers

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Outcomes Following Abiraterone Versus Enzalutamide For Prostate Cancer: A Scoping Review, Yash B, Shah, Amy L. Shaver, Jacob Beiriger, Sagar Mehta, Nikita Nikita, William Kevin Kelly, Stephen J. Freedland, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30-50% vs. 70-75%), slowed progression (HR 0.66; 95% CI 0.50-0.88), and improved overall survival versus AA. ENZ was …

Variation In Molecularly Defined Prostate Tumor Subtypes By Self-Identified Race, Kevin H. Kensler, H. Lee Moffitt Cancer Center And Research Institute, Mohamed Alshalalfa, Bruce J. Trock, Stephen J. Freedland, Michael R. Freeman, Sungyong You, Brandon A. Mahal, Robert Den, Adam Dicker, R. Jeffrey Karnes, Eric A. Klein, Priti Lal, Yang Liu, Elai Davicioni, Walter Rayford, Kosj Yamoah, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

Background: Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men. Objective: To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race. Design, setting, and participants: Five molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID). Outcome measurements and statistical analysis: Differences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic regression …

Gaps In Public Awareness About Brca And Genetic Testing In Prostate Cancer: Social Media Landscape Analysis., Stacy Loeb, Philip Massey, Amy E. Leader, Sameer Thakker, Emily Falge, Sabina Taneja, Nataliya Byrne, Meredith Rose, Matthew Joy, Dawn Walter, Matthew S. Katz, Risa L. Wong, Preethi Selvan, Scott W. Keith, Veda N. Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing, particularly for BRCA1/2, is increasingly important in prostate cancer (PCa) care, with impact on PCa management and hereditary cancer risk. However, the extent of public awareness and online discourse on social media is unknown, and presents opportunities to identify gaps and enhance population awareness and uptake of advances in PCa precision medicine.

OBJECTIVE: The objective of this study was to characterize activity and engagement across multiple social media platforms (Twitter, Facebook, and YouTube) regarding BRCA and genetic testing for PCa compared with breast cancer, which has a long history of public awareness, advocacy, and prominent social media …

Gaps In Public Awareness About Brca And Genetic Testing In Prostate Cancer: Social Media Landscape Analysis, Stacy Loeb, Philip Massey, Amy Leader, Sameer Thakker, Emily Falge, Sabina Taneja, Nataliya Byrne, Meredith Rose, Matthew Joy, Dawn Walter, Matthew S Katz, Risa L Wong, Preethi Selvan, Scott W Keith, Veda N. Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing, particularly for BRCA1/2, is increasingly important in prostate cancer (PCa) care, with impact on PCa management and hereditary cancer risk. However, the extent of public awareness and online discourse on social media is unknown, and presents opportunities to identify gaps and enhance population awareness and uptake of advances in PCa precision medicine.

OBJECTIVE: The objective of this study was to characterize activity and engagement across multiple social media platforms (Twitter, Facebook, and YouTube) regarding BRCA and genetic testing for PCa compared with breast cancer, which has a long history of public awareness, advocacy, and prominent social media …

Reversing The Effects Of Androgen-Deprivation Therapy In Men With Metastatic Castration-Resistant Prostate Cancer, Catherine H Marshall, Jessa Tunacao, Varun Danda, Hua-Ling Tsai, John Barber, Rakhee Gawande, Clifford R Weiss, Samuel R Denmeade, Corinne Joshu

Department of Medical Oncology Faculty Papers

OBJECTIVE: To investigate whether bipolar androgen therapy (BAT), involving rapid cyclic administration of high-dose testosterone, as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) promotes improvements in body composition and associated improvements in lipid profiles and quality of life.

PATIENTS AND METHODS: Men from two completed trials with computed tomography imaging at baseline and after three cycles of BAT were included. Cross-sectional areas of psoas muscle, visceral and subcutaneous fat were measured at the L3 vertebral level. Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire and 36-item short-form health survey were used to assess quality of life.

RESULTS: …

The Quandary Of Dna-Based Treatment Assessment In De Novo Metastatic Prostate Cancer In The Era Of Precision Oncology., Sigve Nakken, Wolfgang Lilleby, Marta D. Switlyk, Karen E Knudsen, Oscar Lilleby, Sen Zhao, Fatemeh Kaveh, Per O. Ekstrøm, Alfonso Urbanucci, Eivind Hovig

Department of Cancer Biology Faculty Papers

Guidelines for genetic testing have been established for multiple tumor types, frequently indicating the most confident molecularly targeted treatment options. However, considering the often-complex presentation of individual cancer patients, in addition to the combinatorial complexity and inherent uncertainties of molecular findings, deriving optimal treatment strategies frequently becomes very challenging. Here, we report a comprehensive analysis of a 68-year-old male with metastatic prostate cancer, encompassing pathology and MRI findings, transcriptomic results, and key genomics findings from whole-exome sequencing, both somatic aberrations and germline variants. We identify multiple somatic aberrations that are known to be enriched in prostate cancer, including a deletion …

The Impact Of Prostate Cancer Treatment On Quality Of Life: A Narrative Review With A Focus On Randomized Data., James M Taylor, Victor E. Chen, Ryan C. Miller, Benjamin A. Greenberger

Department of Radiation Oncology Faculty Papers

Despite excellent oncologic outcomes, the management of localized prostate cancer remains complex and is dependent on multiple factors, including patient life expectancy, medical comorbidities, tumor characteristics, and genetic risk factors. Decades of iterative clinical trials have improved the optimization and utilization of surgical and radiation-based modalities, as well as their combinatorial use with anti-androgen and systemic therapies. While cure rates are high and converging on equivalent disease control should an upfront surgical or radiotherapeutic approach be optimized, the long-term side effects of surgical and radiation-based treatments can differ significantly in nature. Decisions regarding the selection of therapy are therefore best …

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Angiogenin Mrna Expression Levels In Prostate Cancer Tissue, Bowen Yao, Megumi Shigematsu, Phd, Kamlesh Ganesh Pawar, Phd, Venetia Pliatsika, Ms, Yohei Kirino, Phd

Phase 1

Introduction: Prostate cancer is the most commonly diagnosed cancer in men and second leading cause of cancer deaths. Studies have shown that tRNA fragments are upregulated in prostate cancers and play important roles in carcinogenesis. This project looks at how tRNA cleaving enzyme angiogenin expression is regulated in prostate cancer tissues.

Methods: Clinical data and mRNA expression levels of selected tRNA cleaving enzymes were extracted from the TCGA website. mRNAs were sequenced using IlluminaGA_RNASeqV2 at University of North Carolina.

Results: 546 samples from 494 patients, with normal tissue from 53 patients were collected. ANG mRNA levels were lower in patients …

Manipulation Of Genome Integrity Signaling Axes Contributing To Prostate Cancer Aggressiveness, Frank Duan, Veronica Rodriguez-Bravo, Phd

Phase 1

Introduction: Prostate cancer (PC) is one of the leading causes of death in men, and despite current treatment options patients can develop aggressive disease that spreads to other parts of the body. Little research has focused to date on the effect of centrosome biology in the pathogenesis of PC.

Methods: Two metastatic PC cell lines, DU145 and 22Rv1, as well as highly aggressive derivatives generated in Dr. Rodriguez-Bravo lab (docetaxel-resistant; (DR) variants) were compared through various experiments to determine differences in centrosome proteins expression and functionality. All cells (DU145 /DR and 22Rv1 /DR) underwent electroporations with siRNAs to knockout …

Impact Of In-House Specialty Pharmacy On Access To Novel Androgen Axis Inhibitors In Men With Advanced Prostate Cancer, Anna Driscoll, Nathan Handley, Md, Mba, Adam Binder, Siobhan Henry, W. Kevin Kelly, Do

Phase 1

Introduction: Novel androgen axis inhibitors are standard of care treatments in advanced prostate cancer. The billed amounts for these medications are often very high, which may create significant financial toxicity for patients and lead to delays in treatment. Our institution implemented an in-house specialty pharmacy in 2014, that provides these medications and evaluates copay assistance options for all patients. We evaluated the program’s impact on out of pocket cost (OOP) and turnaround time (TAT).

Methods: We reviewed available internal specialty pharmacy records to identify prescriptions for abiraterone or enzalutamide filled between 1/1/17 and 12/31/18. Payments were stratified by primary payment …

Comparison Of Mri- And Trus-Informed Prostate Biopsy For Prostate Cancer Diagnosis In Biopsy-Naive Men: A Systematic Review And Meta-Analysis., Hanan Goldberg, Ardalan E. Ahmad, Thenappan Chandrasekar, Laurence Klotz, Mark Emberton, Masoom A. Haider, Samir S. Taneja, Karan Arora, Neil Fleshner, Antonio Finelli, Nathan Perlis, Mark D. Tyson, Zachary Klaassen, Christopher J.D. Wallis

Department of Urology Faculty Papers

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) with informed targeted biopsies (TGBX) has changed the paradigm of prostate cancer (PCa) diagnosis. Randomized studies have demonstrated a diagnostic benefit of Clinically significant (CS) for TGBX compared to standard systematic biopsies (SBX). We aimed to evaluate whether mpMRI-informed TGBX has superior diagnosis rates of any-, CS-, high-grade (HG)-, and clinically insignificant (CI)-PCa compared to SBX in biopsy-naive men.

METHODS: Data was searched in Medline, Embase, Web of Science, and Evidence-based medicine reviews-Cochrane Database of systematic reviews from database inception until 2019. Studies were selected by two authors independently, with disagreements resolved by consensus …

The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to …

Prevalence Of Suspected Hereditary Cancer Syndromes And Germline Mutations Among A Diverse Cohort Of Probands Reporting A Family History Of Prostate Cancer: Toward Informing Cascade Testing For Men., Thenappan Chandrasekar, Laura Gross, Leonard G. Gomella, Sarah E. Hegarty, Joon Yau Leong, Veda N. Giri

Department of Urology Faculty Papers

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing.

OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands.

DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to …

Impact Of Tumor Regional Involvement On Active Surveillance Outcomes: Validation Of The Cumulative Cancer Location Metric In A Us Population., Joon Yau Leong, Courtney Capella, Seth Teplitsky, Leonard G. Gomella, Edouard J. Trabulsi, Costas D. Lallas, Thenappan Chandrasekar

Department of Urology Faculty Papers

BACKGROUND: Treatment progression for men on active surveillance (AS) for prostate cancer (PCa) is driven primarily by grade and volume progression on isolated prostate biopsies (PBx). As PCa is a multifocal disease, regional disease progression over time should be accounted for.

OBJECTIVE: To validate the utility of the cumulative cancer location (CCLO) metric, which assesses regional core involvement, as described by Erickson et al (Cumulative cancer locations is a novel metric for predicting active surveillance outcomes: a multicenter study. Eur Urol Oncol 2018;1:268-75), in predicting AS outcomes in a North American cohort.

DESIGN, SETTING, AND PARTICIPANTS: A single-institutional retrospective chart …

Mapk Reliance Via Acquired Cdk4/6 Inhibitor Resistance In Cancer., Renée De Leeuw, Christopher Mcnair, Matthew J. Schiewer, Neermala Poudel Neupane, Lucas J. Brand, Michael A. Augello, Zhen Li, Larry C. Cheng, Akihiro Yoshida, Sean M. Courtney, E. Starr Hazard, Gary Hardiman, Maha H. Hussain, J. Alan Diehl, Justin M. Drake, William Kevin Kelly, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Purpose: Loss of cell-cycle control is a hallmark of cancer, which can be targeted with agents, including cyclin-dependent kinase-4/6 (CDK4/6) kinase inhibitors that impinge upon the G₁-S cell-cycle checkpoint via maintaining activity of the retinoblastoma tumor suppressor (RB). This class of drugs is under clinical investigation for various solid tumor types and has recently been FDA-approved for treatment of breast cancer. However, development of therapeutic resistance is not uncommon.

Experimental Design: In this study, palbociclib (a CDK4/6 inhibitor) resistance was established in models of early stage, RB-positive cancer.

Results: This study demonstrates that acquired palbociclib resistance renders cancer …