bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B004: Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2
Authors: Thomas Elizabeth , Thankan Retheesh Sulochana , Purushottachar Puranik , Njar Vincent C.O.
Published: December 2023

Prostate cancer incidence and mortality rates are remarkably higher in African-American (AA) men as compared to their European-American (EA) counterparts even after factoring in socio economic status. The disproportionate incidence of prostate cancer and associated mortality in African men is currently becoming more evident as Several studies have reported significant variations in genetic, molecular, epigenetic, microRNA, and cell signaling pathways in patients of Caucasian and African race. As androgen is implicated in prostate cancer progression and about 90% of the cases are Androgen-dependent, blocking androgen action is an effective strategy in treating prostate cancer. Previously, we reported that galeterone and VNPP433-3β, a next generation galeterone analog potently inhibit metastatic castration resistant prostate cancer of Caucasian origin in vitro and in vivo by degrading AR/AR-V7 and Mnk1/2. Since the prostate cancer patients of African descent express significant levels of AR and Mnk1/2, we investigated the efficacy of galeterone and VNPP433-3β in treating prostate cancer of African men. Cell proliferation assay using the cell lines MDA-PCa 2b and RC77 T/E derived from AA prostate cancer patient demonstrates that galeterone and VNPP433-3β can effectively inhibit prostate cancer of African descent at very low concentration. These cell lines are Androgen-sensitive and further biochemical studies reveal that galeterone and VNPP433-3β degrade AR and Mnk1/2 in RC77 T/E and MDA-PCa 2b cell lines, thereby inhibiting its proliferation. Galeterone and VNPP433-3β significantly decrease the half-life of AR in these cell lines by increasing the rate of ubiquitination and proteasomal degradation of AR. Therefore, galeterone and VNPP433-3β hold significant promise for the clinical management of prostate cancer in patients of African descent

Citation Format: Elizabeth Thomas, Retheesh Sulochana Thankan, Puranik Purushottachar, Vincent C.O. Njar. Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B004.
Abstract B005: In-silico identification of oxa/thiazole carboxamides as potential breast cancer therapeutic agents with vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitory effect
Authors: Ewell Steven M. , Mequanint Getinet , Sikazwe Donald , Redda Kinfe , Mochona Bereket
Published: December 2023

Vascular Endothelial Growth Factor Receptor (VEGFR-2) is a tyrosine kinase receptor mainly known to be expressed in vascular endothelial cells. Overexpression of VEGFER-2 has been linked to tumor angiogenesis, necessitating the need for VEGFER-2 inhibitors. In-silico screening of oxa/thiazole carboxamide scaffold-bearing compounds retrieved from the ZINC database was conducted to identify potential anticancer agents with VEGFR-2 inhibitory effect. The interaction of VEGFR2 with tivozanib was used to generate a six-point pharmacophore model for screening ZINC chemical database. The virtual screening for potential VEGFR2 inhibitors generated 48 hits. The hits were filtered and ranked using molecular docking, drug-likeness, and absorption, distribution, metabolism, and excretion (ADME) protocols. The molecular docking results displayed ten compounds that adapted a similar binding mode and orientation within the active site of the VEGFR2 receptor. The molecular dynamic (MD) simulation analysis of the best hit, 3C, was carried out to validate the docking data. The RMSD and RMSF analysis was used to explain the stability of the VEGFR2 and 3c during the 50 ns simulation trajectory. The MD output revealed that the complex maintained conformational stability and consistent flexibility throughout the run. The results of the docking and simulation techniques supported each other. Thus, 3c emerged as a promising oxa/thiazole carboxamide-carrying lead molecule in our search for potential triple-negative breast cancer therapy.

Citation Format: Steven M. Ewell, Getinet Mequanint, Donald Sikazwe, Kinfe Redda, Bereket Mochona. In-silico identification of oxa/thiazole carboxamides as potential breast cancer therapeutic agents with vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitory effect [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B005.
Abstract B023: Monoclonal gammopathy of undetermined significance and multiple myeloma survival among Hispanics living in Puerto Rico
Authors: Castañeda-Avila Maira , Suárez-Ramos Tonatiuh , Torres-Cintrón Carlos R. , Gierbolini-Bermúdez Axel , Ortiz-Ortiz Karen J.
Published: December 2023

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre-malignant condition that may progress to multiple myeloma (MM). The aim of this study was to investigate the effect of previous MGUS diagnosis on MM survival. Methods: Data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database were analyzed. The study included incident cases of MM diagnosed between 2010 and 2016. Patients with a previous MGUS diagnosis were identified through a claims-based algorithm. Competing-risk modeling was used to estimate the impact of previous MGUS on MM survival, adjusting for sex, age, comorbidity index, and insurance. The results were stratified by sociodemographic characteristics. Results: Of the 1,205 patients diagnosed with MM, 9.7% (n=117) had a previous diagnosis of MGUS. Patients with a previous MGUS diagnosis were found to be older, with a higher comorbidity index, and had Medicare compared to those without a previous MGUS diagnosis. Additionally, these patients were less likely to die from MM (SHR: 0.48, 95%CI=0.33-0.71) than those without a previous MGUS diagnosis. The magnitude of the association between MGUS and MM mortality varied by sociodemographic characteristics. For example, patients between 40-69 years with a previous MGUS diagnosis were less likely to die from MM (SHR:0.23, 95%CI=0.09-0.60) than those without MGUS. Patients with MGUS and ≤1 comorbidity index were also less likely to die from MM (SHR:0.31, 95%CI=0.18-0.55) than those without MGUS with the same comorbidity index. Males with MGUS were less likely to die from MM (SHR:0.41, 95%CI=0.22-0.73), but the association was weaker among females. Patients with MGUS and Medicare were less likely to die from MM (SHR:0.43, 95%CI=0.25-0.74) than those without MGUS who also had Medicare. No significant association was found between MGUS and MM mortality among patients with other insurance types, other age groups, and other comorbidities index. Conclusion: Findings show that males, younger adults, and those with low comorbidity may benefit from a prior MGUS diagnosis, indicating that patients with a previous MGUS diagnosis may have improved survival due to earlier access to more effective treatments for MM. Further research is necessary to gain a comprehensive understanding of the underlying mechanisms.

Citation Format: Maira Castañeda-Avila, Tonatiuh Suárez-Ramos, Carlos R. Torres-Cintrón, Axel Gierbolini-Bermúdez, Karen J. Ortiz-Ortiz. Monoclonal gammopathy of undetermined significance and multiple myeloma survival among Hispanics living in Puerto Rico [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B023.
Abstract B027: Evaluation of dnaja2:A target for chemotherapy sensitization of cancer cells
Authors: Bai Feng , Rozas Hernan Flores
Published: December 2023

Breast cancer is the second most common cause of death from cancer in women in the United States. The disease accounts for 1 in 3 of new female cancers annually. Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer. TNBC is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative providing fewer treatment options and resulting in worse prognosis. There are a variety of chemotherapy drugs used to treat TNBC but they may cause serious side effects which limit their use. Our laboratory has investigated the pathways that protect cells from anthracyclines, a commonly used chemotherapy agent. Through a genetic screening in the yeast S. cerevisiae, we identified YDJ1, which encodes for a gene involved in the heat-shock response pathway, that when inactivated rendered cells over 100-fold more sensitive to doxorubicin. YDJ1 is a homolog of the human gene DNAJA2 (DnaJ homolog subfamily A member 2). The protein encoded by this gene belongs to the DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity of Hsp70 promoting the folding of denatured proteins. We hypothesize that DNAJA2 protects cells from anthracycline exposure. To evaluate the role of DNAJA2 in the sensitivity of cancer cells exposed to doxorubicin, we knocked down DNAJA2 in the TNBC cell line MDA-MB-231 using a lentivirus-based shRNA. Cells were made stably transfected by continued selection with puromycin. Resulting knockdown cells show significant reduction of DNAJA2 protein. In addition, the cells also show accumulation of ROS, decreased cell mobility and decreased resistance to anticancer agents such as doxorubicin. Additional phenotypes are currently under investigation, as well as the interaction of the other members of the DNAJA family of proteins. We hope that our data contributes to the development of protocols to sensitize cancer cells to chemotherapy.   Funding provided by the Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center. Tissue Modeling Core. U54CA233396, subproject 6636

Citation Format: Feng Bai, Hernan Flores Rozas. Evaluation of dnaja2:A target for chemotherapy sensitization of cancer cells [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B027.
Abstract B041: Understanding T-cell large granular lymphocytic leukemia: Diagnosis and treatment options
Authors: Khan Aliya M. , Patterson Kierston R. , Patel Raj , Urisote Sophia Navajas
Published: December 2023

Introduction: T-cell large granular lymphocytic leukemia, or T-LGL leukemia, is rare cancer affecting T-cells and natural killer cells. It is characterized by the abnormal proliferation of mature T-cells expressing specific markers. Standard treatments involve immunosuppressive therapies. Understanding the diagnosis and treatment options is crucial for optimal care. Case Presentation: A 54-year-old male with chronic anemia and iron overload was initially diagnosed with myelodysplastic syndrome (MDS). Vidaza followed treatment with Danazol due to negative MDS and myeloproliferative neoplasm (MPN) results. Concerns of red cell aplasia led to corticosteroid and cyclosporin administration, discontinued during the COVID-19 outbreak. A subsequent biopsy revealed pure red cell aplasia, and the patient was prescribed Cyclosporin and later switched to Danazol. The patient underwent Anti-Thymocyte Globulin (ATG) treatment at a cancer center. A bone marrow biopsy confirmed T-LGL leukemia with abnormal CD8-positive T-cells. PCR analysis confirmed clonal T-cell proliferation. Cytogenetics and mutation analyses were negative. The patient is currently receiving Cyclosporin, prednisone, and Jadenu. Conclusion: This case highlights the challenges in diagnosing and managing T-LGL leukemia, a rare lymphoproliferative disorder. The patient's complex medical history and mimicking of other hematologic disorders underscore the need for a multidisciplinary approach. Individualized therapy based on clinical response is necessary due to limited treatment options. Further research and prospective trials are essential to establish a standard of care.

Citation Format: Aliya M. Khan, Kierston R. Patterson, Raj Patel, Sophia Navajas Urisote. Understanding T-cell large granular lymphocytic leukemia: Diagnosis and treatment options [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B041.
Abstract B048: Disparities in treatment course and outcomes in females diagnosed with non-metastatic inflammatory breast cancer
Authors: Lung Kirsten , Sheng Young , George Brandon , Willis Alliric , Lazar Melissa
Published: December 2023

Background: Inflammatory breast cancer (IBC) is an uncommon, aggressive disease with a poor prognosis. National treatment guidelines recommend neoadjuvant chemotherapy followed by modified radical mastectomy (MRM) and radiation. Disparities in treatment may contribute to survival differences, and few studies have assessed factors contributing to such variation. We aimed to identify demographic and facility differences in treatment and survival among females with non-metastatic IBC. Methods: Secondary analysis of the National Cancer Database (2012-2016) on females diagnosed with non-metastatic IBC was performed. Demographics, treatment, and facility data were collected. Statistical analysis was performed with SAS. Results: A total of 5,438 patients met the inclusion criteria. Receiving surgical intervention was associated with age (p<0.0001), race (p<0.0001), and facility (p=0.03), with increased odds of surgery for younger, white, and comprehensive community cancer program patients. Receiving radiation therapy was associated with age (p <0.0001) and race (p<0.0001), with decreased odds of radiation for older, Black, and Hispanic patients. Receiving chemotherapy was associated with age (p <0.0001), with increased odds of chemotherapy for younger patients. Days from diagnosis to treatment initiation was associated with race (p<0.0001) and facility (p=0.0089), with increased time for Black, Hispanic, and academic facility patients. Survival time was associated with age (p<0.0001), race (p<0.0001), facility (p=0.0002), Charlson-Deyo (CD) score (p<0.0001), and surgery (p<0.0001), with decreased survival for older, Black, non-academic facility, higher CD score, and non-surgery patients. Conclusions: Treatment trends and survival of IBC patients are impacted by sociodemographic and facility-level variation, which, when addressed, may help to improve patient outcomes.

Citation Format: Kirsten Lung, Young Sheng, Brandon George, Alliric Willis, Melissa Lazar. Disparities in treatment course and outcomes in females diagnosed with non-metastatic inflammatory breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B048.
Abstract B063: Association of genetic ancestry with all-cause mortality and cancer mortality among Black and White individuals in the PLCO cohort
Authors: Dill Courtney D. , Crump Dontray , Landy Rebecca , Cheung Li , Huang Wen-Yi , Berndt Sonja , Freedman Neal , Katki Hormuzd
Published: December 2023

Introduction: It is unknown how much of the increased all-cause mortality and cancer mortality risk in Black individuals is due to race as a social construct versus biological factors such as genetic ancestry. We examined the association of genetic ancestry with all-cause mortality and cancer mortality, controlling for risk factors and self-reported race/ethnicity, in the PLCO cohort. Methods: We used PLCO data from 154,887 participants, including 7,708 Black individuals and 137,562 White individuals. Genetic ancestry was determined by GRAF (https://github.com/ncbi/graf) on a set of 10,000 pre-selected fingerprinting variants. Percent ancestry for each of Europe, Africa, and East-Asia was determined for each person. We fit Cox models for time to death or time to cancer death, controlling for smoking history and other risk factors. Results: Self-reported Black individuals had increased all-cause mortality (HR=1.27, 95%CI: 1.19-1.35, p<0.0001) and cancer mortality (HR=1.25 95%CI: 1.12-1.40, p<0.0001) versus self-reported White individuals. For White individuals, increases in European ancestry were associated with increased death risk, (HR=1.01 per 1% increase in European ancestry, 95% CI:1.01-1.02, p=0.0003) and cancer mortality (HR=1.01, 95%CI:1.00-1.02, p=0.02). For Black individuals, increases in African ancestry were also associated with increased death risk, (HR=1.01 per 1% increase in African ancestry, 95%CI: 1.00-1.01, p=0.01) and cancer mortality (HR=1.01, 95%CI: 1.00-1.04, p=0.13), although not statistically significant. Conclusions: For self-reported White individuals, increasing European ancestry was associated with an increased all-cause mortality and cancer mortality risk. For self-reported Black individuals, there was evidence that increasing African ancestry increases all-cause mortality risk, but not cancer mortality. However, associations with ancestry were small and may be vulnerable to residual confounding. Impact/Significance: A mechanistic explanation for this finding is unclear, but it could be related to population genetic “fitness” with reduced genetic admixture leading to decreased fitness for survival.

Citation Format: Courtney D. Dill, Dontray Crump, Rebecca Landy, Li Cheung, Wen-Yi Huang, Sonja Berndt, Neal Freedman, Hormuzd Katki. Association of genetic ancestry with all-cause mortality and cancer mortality among Black and White individuals in the PLCO cohort [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B063.
Abstract B100: Using a plant-based diet and exercise to improve outcomes in African American postmenopausal breast and endometrial cancer survivors
Authors: Rivers Desiree A. , Leonis Regina , Abdul-Hameed Zakirah A. , Singh Shaliesh A. , Rivers Brian A.
Published: December 2023

Background:  Obese postmenopausal African American (AA) women with breast and endometrial cancer are at increased risk of recurrence. Obesity and aging have been associated with changes in the gut microbiota. Plant-based diets, such as soy isoflavone consumption may protect against breast and endometrial cancer.   Methods:  A mixed-methods, lifestyle intervention study was conducted to evaluate adoption of a whole-food plant-based diet, physical activity, and changes in risk for breast and endometrial cancer among obese, post-menopausal AA women.  We examined acceptability and feasibility of adopting a whole-food, plant-based diet and the effect of the diet on reductions in weight, adiposity, inflammation, circulating estrogen, and gut microbiome profile. Results:  In 5 focus group discussions, 20 AA women described their knowledge of breast and endometrial cancer risk factors, attitude toward a plant-based diet, experience with making lifestyle changes, and preferences for plant-based alternatives to traditional meat-based meals.  This feedback was used to tailor the 4-weeks of plant-based produce boxes provided to the women.  Women report being pleased with the food selections; document adherence to the meals and physical activity with food and exercise tracking.  Gut microbiome analysis is underway. Conclusion:  This study addresses knowledge gaps in breast and endometrial cancer risk and behavioral modifications affecting risk among an obese, post-menopausal AA female population.  The long-term goal of this program of research will shed light on the mechanisms involved in the gut microbiome and the contributions of changes to these systems on declining health.

Citation Format: Desiree A. Rivers, Regina Leonis, Zakirah A. Abdul-Hameed, Shaliesh A. Singh, Brian A. Rivers. Using a plant-based diet and exercise to improve outcomes in African American postmenopausal breast and endometrial cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B100.
Abstract C092: Genetic profiling of high grade serous ovarian cancer among women of African ancestry
Authors: Omotoso Ayodele , Ezenkwa Uchenna , Butler Raleigh , Castillo Melissa , Sanchez-Covarrubias Alex , Schlumbrecht Matthew , Pinto Andre , Audu Bala , George Sophia
Published: December 2023

(A) AN INTRODUCTORY SENTENCE INDICATING THE PURPOSES OF THE STUDY:    Ovarian cancer (OC) is a heterogeneous disease with high grade serous ovarian cancer (HGSOC) as the commonest, the most aggressive tumor, which is often diagnosed at advanced stages, and with poor overall survival. Unfortunately, like many other cancer diagnoses, women of West African ancestry (Black women) with ovarian cancer experience worse outcomes than White women. In the US, Black women have higher morbidity and mortality rates and higher un-staged or unclassified tumors compared with White women, resulting in undertreatment with subsequent compromise in progression-free survival. Genomic instability is one of the most common underlying features of ovarian cancer and defective DNA damage repair has been implicated. The goal is to uncover canonical genes associated with the aggressive behavior of HGSOC in a cohort of black women that could explain the biology of this tumor. (B) A BRIEF DESCRIPTION OF PERTINENT EXPERIMENTAL PROCEDURES:   Formalin fixed paraffin embedded (FFPE) HGSOC tissue blocks from Nigeria in West Africa (WAB), Bahama in Caribbean (CBB), and Miami in USA (USB) were identified and selected after rigorous review and confirmation with immunohistochemical (IHC) markers when needed. Integration of digital histopathology and IHC markers (estrogen receptor, progesterone receptor, Ki67 and P53), whole exome sequence, RNA sequence of the FFPE samples was used to identify the proportion of genomic instability and defective DNA damage repair genes. We use spatial genomic library on tissue microarray (TMA) slide prepared on GeoMx digital spatial profiler (DSP) Nanostring platform to study the biology of the tumor and the tumor microenvironment (TME) and proteogenomics.(C) A SUMMARY OF THE NEW, UNPUBLISHED DATA:   The unsupervised principal component analysis of the tumor showed a distinct population of WAB and USB while the CBB showed admixture population. BACH2, ARG1, NAFT2 and FRA10A1 are commonly differentially expressed genes among the cohort. There is low expression of routine IHC markers among the WAB compared to the other groups.     Conclusion:   There is variation on gene expression by nativity and we hope to explore this variation for therapeutic purpose among black women with ovarian cancer.  

Citation Format: Ayodele Omotoso, Uchenna Ezenkwa, Raleigh Butler, Melissa Castillo, Alex Sanchez-Covarrubias, Matthew Schlumbrecht, Andre Pinto, Bala Audu, Sophia George. Genetic profiling of high grade serous ovarian cancer among women of African ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C092.
Abstract C137: Action-based modeling for national Indigenous cancer care partnerships: Patient navigation services, health policy, and sustainability
Authors: Roybal Carmela M. , Haring Rodney C.
Published: December 2023

Cancer-specific, Indigenous led patient navigation systems are often a gap for Indigenous communities. These communities often face greater cancer health disparities and increased mortality due to late-stage diagnoses. Early detection and navigation are key to life-saving treatment. This quality improvement study shares the foundations for implementation of an Indigenous/rural patient navigation program. The discussion shapes planning and evaluative efforts for the build out of a memorandum of understanding from an NCI-Designated cancer center’s Indigenous cancer service arm (Northeast) towards expansion to an Indigenous community-driven university-based Native American budget and policy institute (Southwest).  Program development centers Indigenous underpinnings of wampum agreements, Pueblo cane agreements, tribal sovereignty, and governance. Findings include translational modeling of Indigenous based cancer focused patient navigation successes, robust cross-training collaborations, inter-tribal resource building, incorporation of virtual patient navigation, grass-root partnerships, Indigenous-led community outreach, and health policy development.

Citation Format: Carmela M. Roybal, Rodney C. Haring. Action-based modeling for national Indigenous cancer care partnerships: Patient navigation services, health policy, and sustainability [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C137.
Abstract IA011: The burden of cancer across Sub-Saharan Africa is projected to continue to rise, however, cancer care services are out of reach for most patients
Authors: Shinkafi-Bagudu Dr. Zainab
Published: December 2023

The global burden of cancer is increasingly borne by patients in the low- and middle-income countries. The International Agency for Research on Cancer predicts that by 2030, the global burden of cancer will reach 21.4 million and the annual number of cancer deaths worldwide will reach 13.2 million. “Annual cancer deaths in sub-Saharan Africa (SSA) could reach 1 million by 2030, nearly double the 520,000 deaths from cancer that occurred in 2020. Cancer incidence is also projected to double by 2040 to more than 1.4 million cases per year, without rapid interventions, according to a new Lancet Oncology Commission.” For the above reasons, the need to prioritize and decentralize cancer control in low- and middle-income countries cannot be overemphasized. Accelerating cancer control in low resource settings demands concerted effort that is global, national, and local.

Citation Format: Dr. Zainab Shinkafi-Bagudu. The burden of cancer across Sub-Saharan Africa is projected to continue to rise, however, cancer care services are out of reach for most patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA011.
Abstract IA018: Sexual orientation and gender identity (SOGI) collection: Experiences at an NCI-Designated Cancer Center
Authors: Schabath Matthew B.
Published: December 2023

Wide-spread collection of sexual orientation and gender identity (SOGI) data has been a barrier to conduct of research to identify disparities and inequitable cancer care among sexual and gender minority (SGM) populations. Additionally, lack of SOGI data in electronic health records (EHR) renders clinical care teams unable to integrate such information into appropriate and tailored care and treatment plans and may delay the establishment of respectful, affirming, and knowledgeable relationships between patients and their cancer care teams, and the institutions in which they receive health care. The absence of SOGI data in EHRs also prevents the identification of individuals from SGM groups for inclusion into clinical trials to improve and strengthen the evidence-base for clinical treatment of cancer, from prevention through survivorship. Despite many organizations urging improvement in evidence-based cancer care for SGM populations, satisfactory progress has not yet been achieved in part attributed to the lack of widespread SOGI collection in medical records. As a first step in identifying and remedying real-world disparities and inequity among SGM populations, the H. Lee Moffitt Cancer Center & Research Institute (Tampa, FL) began collecting sexual orientation in 2016 and gender identity in 2017 as standard-of-care demographic items for all new patients.  Moffitt Cancer Center is one of the first NCI-Designated Cancer Centers to collect SOGI as standard-of-care demographics for all patients.  All new patients are required to complete the web-based electronic patient questionnaire prior (EPQ) to, or on the day of, their first visit. EPQ data are integrated into the EHR, and available at the point of care.  To date, SOGI demographics have been collected on over 150,000 patients and ~3.5% of our patient population are self-identified as a SGM. Leveraging this valuable and largely unique data resource among NCI-Designated Cancer Centers, we have already identified real-world disparities and inequity among SGM persons with cancer. Additional research is underway to address issues related to intersectionality and to identify barriers to improve SOGI disclosure.  In this session, we will present our approach to implement institutional-side SOGI collection and dispel myths about the difficulties and barriers to implementing SOGI data collection.

Citation Format: Matthew B. Schabath. Sexual orientation and gender identity (SOGI) collection: Experiences at an NCI-Designated Cancer Center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA018.
Abstract IA029: Expanding access and participation to early phase clinical trials for our underrepresented populations
Authors: Baranda Joaquina C.
Published: December 2023

The American Society of Clinical Oncology (ASCO) has a firm position that phase I trials provide trials participants potential benefit with improved quality of life, psychological and direct medical benefit. Disproportionate access to novel therapies through early phase clinical trials among underrepresented populations continues to exist.  In fact, there is worsening disparity in accrual of patients from racial and ethnic minority groups in phase 1 trials of drugs for metastatic cancer. Access to cutting-edge clinical trials leading to paradigm-changing treatments is critical for cancer care and equity in society, as participation in clinical trials correlates with reduction in mortality. Stark disparities in access and participation to clinical trials impact underserved populations among racial and ethnic minorities, socioeconomically disadvantaged, and geographically isolated populations. The impact of newer therapies, if inadequately studied in underserved populations, may result in poor generalizability of study results and uncertain benefit for these groups. Further, evidence suggests that access to clinical trials narrows the gap in cancer care disparity among patients in urban and rural communities. In response to ethical, clinical, and biologic mandate, the National Cancer Institute’s (NCI) Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP.2020) was created. This congressional mandate was a P30 administrative supplement awarded to eight NCI-designated cancer centers to enhance access to early phase precision medicine Experimental Therapeutics Clinical Trials Network (ETCTN) clinical trials for minority and underserved populations. The purpose of this presentation is to share best practices learned in CATCH-UP.2020 and discuss how this program helped create a roadmap to building a clinical trials ecosystem that allowed expanded access to early phase trials through cross-fertilization of successful tools among the CATCH-UP sites and within ETCTN. In our institution, learned best practices are applied across the spectrum of early phase clinical investigations to help overcome clinical trials disparities using the rural lens. With the goal of bringing precision medicine clinical trials close to home for our underrepresented populations, we aim to accelerate drug development without leaving anyone behind.

Citation Format: Joaquina C. Baranda. Expanding access and participation to early phase clinical trials for our underrepresented populations [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA029.
Abstract A006: Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy
Authors: Sharma Priya Chandramohan , Patel Digna , Dalai Sarat K
Published: December 2023

Autologous cell-based therapy is a preferred approach for Cancer immunotherapy. However, generating potent NK cells and antigen experienced T cells has been a challenge. To address this issue, we have developed a strategy of using the combination of IL-12 and IL-15 to activate CD4+ T cells, CD8+ T cells and NK cells. IL-12 and IL-15 possess distinct roles but both are potent inflammatory cytokines. IL-12 is a vital promoter of Th1 differentiation via activation of signal transducer and activator of transcription 4 (STAT4), while IL-15 is essential for developing innate immune response as well as contributing to the maintenance of memory CD8+ T cells. Substantial in vivo and in vitro data have been reported to support the role of IL-15 as a T cell growth factor. These activities of IL-12 and IL-15 make them ideal for combinatorial immunotherapy of cancer. However, the short half-life (~ 1hr) and poor bioavailability limits the therapeutic use of IL-15. To overcome these limitations, we have designed chimeric IL-15-IgG2 (Indian Patent Application No. 201721010096A) with an objective of augmenting the generation of memory T cells as well as reactivating them during the antigenic challenge. Our stable chimeric IL-15 has a half-life of >40 Hrs. In humans, IL-12 is needed for DCs to provoke rapid IFN-g production by NK cells, IL-15 seems essential for the NK cell proliferation. In the present study, we are testing the potential of chimeric IL-15 individually and in combination with native hIL-12 as an activator of CD4+ T cells, CD8+ T cells and NK cells. The combination of both cytokines shows potent release of IFN-g as well as activation of the T-cell subsets and NK cells. In our future studies we will use these pre-activated cells for adoptive transfer in cancer immunotherapy. Detailed findings will be reported during the conference.

Citation Format: Priya Chandramohan Sharma, Digna Patel, Sarat K Dalai. Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A006.
Abstract A015: Rapid mitochondrial reactive oxygen species production precedes NF-κB activation and pro-inflammatory responses in macrophages
Authors: Zaniani Parinaz Tavakoli , Balomenos Dimitrios
Published: December 2023

Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, we performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, MAPK activation by regulating TRAF-6 ubiquitination, and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies, targeting early mROS production and control extreme inflammation in the context of sepsis and other inflammatory diseases.

Citation Format: Parinaz Tavakoli Zaniani, Dimitrios Balomenos. Rapid mitochondrial reactive oxygen species production precedes NF-κB activation and pro-inflammatory responses in macrophages [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A015.
Abstract A034: VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity
Authors: Rezaei Reza , Azad Taha , Petryk Julia , Bell John C.
Published: December 2023

This research introduces VV-iVP55, a conditionally replicating vaccinia virus platform, as a promising alternative to thymidine kinase (Tk) deleted oncolytic vaccinia viruses. The unique feature of VV-iVP55 is its growth control using doxycycline, a trait not found in conventional Tk-deleted viruses. Laboratory studies revealed that VV-iVP55 achieves higher virus titers and lower cell viability in B16-F10 and MC38 syngeneic models compared to Tk-deleted viruses. Notably, VV-iVP55 demonstrated lower toxicity in immunocompromised mice upon doxycycline withdrawal, unlike Tk-deleted viruses that showed significant toxicity. In vivo efficacy studies further highlighted the superiority of VV-iVP55 over Tk-deleted viruses in CT26 and B16 subcutaneous models, as well as MC38 subcutaneous and intraperitoneal models. An immune microenvironment analysis conducted six days post-intratumoral injection revealed beneficial alterations induced by VV-iVP55, such as increased T and B cell content in the tumor and reduced MDSCs in both the tumor and spleen. Moreover, VV-iVP55 was linked to a significant change in T cell differentiation. Unlike the PBS and Tk viruses, which showed almost complete differentiation towards effector T cells, VV-iVP55 maintained a substantial population of T cells in naive and transition phases, significantly in both CD4 and CD8 T cells. This likely led to lower expression of exhaustion markers PD1, TIM3, TIGIT, and LAG3, suggesting less exhaustion and more potential for immune response. In summary, VV-iVP55 emerges as a powerful alternative to Tk-deleted oncolytic vaccinia viruses, offering enhanced immunogenicity, controlled toxicity, and preserved oncolytic properties.

Citation Format: Reza Rezaei, Taha Azad, Julia Petryk, John C. Bell. VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A034.
Abstract B032: CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy
Authors: Cha Junha , Kim Dahee , Kim Gamin , Cho Jae-Won , Sung Euijeong , Baek Seungbyn , Hong Min Hee , Kim Chang Gon , Sim Nam Suk , Hong Hyun Jun , Lee Jung Eun , Hemberg Martin , Park Seyeon , Yoon Sun Ock , Ha Sang-Jun , Koh Yoon Woo , Kim Hye Ryun , Lee Insuk
Published: December 2023

Oropharyngeal squamous cell carcinoma (OPSCC) is a prevalent subtype of head and neck cancer representing one of the largest diagnosed malignancies worldwide. A distinct subtype of OPSCC induced by Human Papilloma Virus (HPV) is well known to favor beneficial clinical outcomes in cancer treatment compared to HPV-negative OPSCCs. However, HPV-positive OPSCCs in the context of immunotherapy remains unclear, as no distinct benefits are observed in clinical trials. In this study, we performed single-cell RNA and T cell receptor sequencing analyses of 20 tumor samples to dissect the cellular and molecular factors associated with viral infection and immunotherapy outcome. We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. This finding suggests heterogeneity of malignant cells negates immunotherapy response in HPV-positive OPSCCs. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed significant association with dampened antitumor activity in HPV-positive OPSCC patients, which may explain their clinical heterogeneity. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Validation in an independent cohort confirms enhanced tertiary lymphoid structure activity in HPV-positive OPSCCs. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade confirmed an inverse correlation between the density of CD161+ Trm and changes in tumor size. These results suggest that targeted inhibition of CD161 in Trm may augment immunotherapy efficacy in HPV-positive oropharyngeal cancers.

Citation Format: Junha Cha, Dahee Kim, Gamin Kim, Jae-Won Cho, Euijeong Sung, Seungbyn Baek, Min Hee Hong, Chang Gon Kim, Nam Suk Sim, Hyun Jun Hong, Jung Eun Lee, Martin Hemberg, Seyeon Park, Sun Ock Yoon, Sang-Jun Ha, Yoon Woo Koh, Hye Ryun Kim, Insuk Lee. CD161+ TRM cells counteract HPV-associated clinical benefits in oropharyngeal cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B032.
Abstract B054: Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma
Authors: Vosahlikova Sarka , Holicek Peter , Moserova Irena , Orsulic Sandra , Mikyskova Romana , Hensler Michal , Kasikova Lenka , Lanickova Tereza , Novotny Ondrej , Reinis Milan , Drozenova Jana , Ryska Ales , Rob Lukas , Halaska Michael J , Cibula David , Spisek Radek , Fucikova Jitka
Published: December 2023

Epithelial ovarian carcinoma (EOC) is among the top five causes of cancer-related death in women. Most women with EOC achieve indeed complete remission after primary or interval cytoreductive surgery combined with chemotherapy based on a platinum-taxane doublet. Homologous recombination (HR) defects imposed by germline or somatic BRCA1 DNA repair-associated (BRCA1) or BRCA2 mutations are not only key determinants of platinum sensitivity in EOC patients but also provide a strong rationale for maintenance therapy based on poly(ADP-ribose) polymerase (PARP) inhibitors, which is generally associated with improved progression-free survival (PFS). Besides direct cytotoxic and cytostatic properties, PARPi have been shown to mediate multipronged immunostimulatory effects, largely reflecting their ability to inhibit DNA repair in malignant cells and indicating the possibility to synergy with immune-check point inhibitors (ICIs). Here, using multiparametric flow cytometry, multiplex immunostaining, single cells transcriptomics and functional studies in experimental syngeneic BR5-Akt mouse model and EOC tumor samples, we discuss PARPi immunomodulatory activity, with a specific focus on molecular and cellular pathways that can be harnessed to develop superior combinatorial regimens for clinical management. Thus, PARPi might enhance the mutational load of EOCs as consequence of unrepaired DNA damage and DAMPs exposure, favoring T cell infiltration, but also appear to drive robust type I IFN secretion downstream of cyclic GMP-AMP synthase and stimulator of IFN response cGAMP interactor 1 activation. In addition, the combination of PARPi with ICIs positively regulate the balance between adaptive anti-tumor immunity and innate myeloid components and significantly improve the cytotoxic T cell profile as shown in both experimental mice model and HGSOC tumor samples. We surmise that rationally designed combinations of PARPi and immunotherapeutic agents might be critical to unlock immunosuppression in the EOC microenvironment in support of clinical efficacy.

Citation Format: Sarka Vosahlikova, Peter Holicek, Irena Moserova, Sandra Orsulic, Romana Mikyskova, Michal Hensler, Lenka Kasikova, Tereza Lanickova, Ondrej Novotny, Milan Reinis, Jana Drozenova, Ales Ryska, Lukas Rob, Michael J Halaska, David Cibula, Radek Spisek, Jitka Fucikova. Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B054.
Perspectives of Emergency Medicine Physicians on Hidradenitis Suppurativa Care
Authors: Atluri Swetha , De Devea R. , Shih Terri , Dagenet Caitlyn B. , Masson Rahul , Tran Khiem A. , Ng Vivienne , Hsiao Jennifer L. , Shi Vivian Y.
Published: December 2023

Introduction: Hidradenitis suppurativa (HS) is a chronic skin condition that often requires acute care during periods of flares, with many patients visiting the emergency department over 5 times before receiving a proper diagnosis. However, little is known about emergency medicine (EM) providers’ experiences and knowledge of HS management. Methods: In this study, an anonymous survey was distributed to EM providers to identify knowledge and practice gaps in HS care. Results: The results showed that most respondents lacked confidence in HS diagnosis and management, especially in knowing available treatment options and managing patients with moderate to severe HS. Attendings were more confident than non-attendings in diagnosing and managing HS, and providers who saw more HS patients per month were more confident in referring patients to appropriate specialists. Over 80% of respondents referred HS patients to dermatology, which is an important initial step in HS management. Conclusion: The study highlights the importance of educating EM providers in HS recognition, timely referral to dermatology, and initial management to improve quality of life among patients and mitigate disease progression.