bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B011: FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations
Authors: Sharma Hemakshat , Arreola Alyssa Maria , Heredia Frances L. , Franco Hector L. , Dutil Julie
Published: September 2024

Forkhead box A1 (FOXA1) acts as a pioneer factor for Estrogen Receptor alpha (ERα), playing a crucial role in determining where ERα binds to DNA and regulates gene expression in breast cancer cells. A pioneer factor is a class of transcription factors (TF) that is responsible for opening the chromatin to allow other TFs to attach and activate transcription of that gene. FOXA1 acts as a facilitator for ERα-DNA interactions. It binds to specific DNA regions, opening the chromatin for ERα to bind. It “pre-marks” these sites in the genome even in the absence of estrogen. In fact, FOXA1 is frequently overexpressed in ER+ breast cancers, suggesting it has a crucial role in driving tumor growth. As such, FOXA1 is an attractive therapeutic target that already serves as a great biomarker for many types of breast cancers. Inhibiting FOXA1 can potentially block ER activity and inhibit growth of ER+ breast cancer, especially in those resistant to anti-estrogen therapies, such as tamoxifen. In this project, we identified sites that FOXA1 opens and correlated them with SNP mutations commonly found in the Hispanic population. The presence of these SNPs portends a worse outcome in Hispanic patients. To assess which open chromatin regions are crucial for breast cancer pathogenesis, a ChIP-seq analysis was done on vehicle-treated and estrogen-treated samples to determine FOXA1 binding sites. After identifying gained, lost, and differentially expressed peaks set, these were compared to genome-wide association studies (GWAS) of Hispanic patients to develop an understanding of how much overlap is common between sites of mutations and open sections of chromatin due to FOXA1. Through our analysis, we uncovered a subset of FOXA1 binding sites that overlap with sites of inherited mutation in Hispanic patients. This informs on the subset of genes that are linked to breast cancer and potential therapeutic targets.

Citation Format: Hemakshat Sharma, Alyssa Maria Arreola, Frances L. Heredia, Hector L. Franco, Julie Dutil. FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B011.
Abstract B012: Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data
Authors: Smith Leslie A. , Graim Kiley , Cahill James A.
Published: September 2024

95% of sequencing data is from individuals of European descent. Underrepresentation of non- European individuals in genomic resources has limited our understanding of the effects of population-specific variants on complex traits and disease. Human populations have undergone selection for variants beneficial to survival in their environment, resulting in individuals with genetic variants unique to their ancestral populations. While these variants can impact disease occurrence and treatment outcome, genetic ancestry is often unaccounted for in disease modeling. Lack of ancestral population representation in data has led to disparate disease outcomes and treatment. While the primary proposed solution to this problem is more diverse sequencing of patients, these efforts will take years of effort and continual work to maintain the diversity balance. Additionally, they will not solve the issue; clinical trials cannot expect to capture human global diversity at every stage. Here we show we can mitigate data bias by utilizing readily available genomic population databases to target genes with ancestrally relevant variations. Our AI model, PhyloFrame, creates equitable gene signatures from transcriptomic input data. PhyloFrame corrects for ancestral bias in data by utilizing genomic population databases and functional interaction networks to identify genes both relevant to disease and associated with a variant unique to a single ancestry. PhyloFrame uses gnomAD data to quantify genome-wide ancestry-specific allele frequencies from a large cohort of healthy individuals, which PhyloFrame uses to create ancestry-agnostic signatures when modeling disease data. Our model demonstrates the utility of including readily available population-level data from healthy individuals in AI methods to overcome existing genomic data bias. PhyloFrame serves also as a demonstration of how equitable AI methods create gene signatures applicable across ancestries without requiring sample-specific ancestry information. Our model demonstrates how AI can be used to help mitigate ancestral bias in genomic data using preexisting data and contribute to equitable representation in medical research.

Citation Format: Leslie A. Smith, Kiley Graim, James A. Cahill. Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B012.
Abstract B020: Do U.S. quitsites present information related to providing services for LGBTQ individuals? An audit study
Authors: Ramos Santiago Jeffrey Wilmer , McIntosh Scott , Orfin Rafael , Lara Daimarelys , Joseph Skylar , Kaur Manpreet , Ramos-Pibernus Alixida , Cupertino Ana Paula , Ossip Deborah , Cartujano-Barrera Francisco
Published: September 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR016) of the Conference Program/Proceedings.

Citation Format: Jeffrey Wilmer Ramos Santiago, Scott McIntosh, Rafael Orfin, Daimarelys Lara, Skylar Joseph, Manpreet Kau1, Alixida Ramos-Pibernu3, Ana Paula Cupertin1, Deborah Ossip, Francisco Cartujano-Barrera. Do U.S. quitsites present information related to providing services for LGBTQ individuals? An audit study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B020.
Abstract B041: Community-based prostate cancer screening for Black men
Authors: Cooper Pam , Carter-Wicker Kitty , Stanley Eddie R. , Boyd Imani A. , Mavingire Nicole , Rivers Brian , Kimbro K. S. , Kittles Rick A. , Woods-Burnham Leanne
Published: September 2024

PURPOSE: The 5-year relative survival rate for men with prostate cancer (PC) is greater than 99% when diagnosed at an early stage. The prognosis is much worse for men diagnosed with advanced disease as there is no cure for metastatic PC. With the establishment of prostate- specific antigen (PSA) blood testing as an effective tool for early screening for PC, the prevention of morbidity and mortality from this disease proves possible. However, Black men are more likely to develop aggressive PC and die, yet less likely to be screened despite population-specific guidelines recommending shared decision-making for high-risk groups to begin at age 40. For these reasons, increasing the rate and reach of PSA screening within the community is an innovative approach to raise awareness and reduce mortality from PC for Black men. METHODS: Morehouse School of Medicine’s (MSM) Prostate Cancer Precision Prevention Program (PCP3) leverages community partnerships to provide point-of-care PSA testing at no cost to Black men in the greater Atlanta area and rural Georgia. Community-based screening events were initiated in June 2023 and have been conducted in collaboration churches, municipalities, and non-profit organizations. Participants were recruited at these events and consented to provide one tube of blood drawn by MSM phlebotomists and registered nurses for quantification of PSA levels. Results were processed through Morehouse Healthcare and participants were contacted with individual results and provided with options for follow-up. RESULTS: To date, PCP3 has conducted more than three dozen community-based screening events. Over 1000 Black men have received PSA testing with variable results. CONCLUSION: PCP3 has provided awareness and PSA testing to over 1000 Black men in Atlanta and rural Georgia at higher risk for aggressive and lethal PC. PCP3 aims to assess whether community- based screening reduces mortality from PC for Black men in Georgia over the next few years.

Citation Format: Pam Cooper, Kitty Carter-Wicker, Eddie R. Stanley, Imani A. Boyd, Nicole Mavingire, Brian Rivers, K. S. Kimbro, Rick A. Kittles, Leanne Woods-Burnham. Community-based prostate cancer screening for Black men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B041.
Abstract B111: A needs assessment of genetic and hereditary breast cancer awareness in Southern California women diagnosed with a genetic mutation
Authors: Ruiz Dayanara
Published: September 2024

Background: Breast cancer is a global public health dilemma, considering the public awareness the issue has garnered over the years it continues to be diagnosed in advanced stages. Genetic mutations can increase the risk of developing breast cancer. Literature findings have identified the lack of knowledge surrounding genetic breast cancer susceptibility. Methods: In partnership with Southern California Chapter of The Breasties (SoCal Breasties), an all inclusive nonprofit organization that creates a community for survivors, previvors, thrivers, and caregivers impacted by breast and gynecological cancers, 20 women with a breast cancer related genetic mutation diagnosis were surveyed in a cross-sectional study to determine the need for health education on breast cancer genetic susceptibility. Of the 20 women surveyed, the racial/ethnic identities of the respondents is as follows: 10% identified as Asian American/Pacific Islander; 5% identified as Black; 35% identified as Hispanic/Latinx; 5% identified as “Mixed Race: Black, White”; 40% identified as White; and 5% identified as Ashkenazi Jewish, White. Results: 70% of survey respondents identified not having adequate knowledge of genetic breast cancer susceptibility prior to diagnosis. When looking at racial and ethnic groups, Black, Hispanic/Latinx, and Asian American/Pacific Islander women made up 71% of the population that lacked proper knowledge of the topic when compared to their white counterparts. 75% identified health education as the most needed resource for genetic breast cancer susceptibility. When asked to share one piece of insight, the most common sentiment expressed was “Knowledge is Power.”Conclusions: There is a need for greater health education on genetic breast cancer susceptibility, especially in racial and ethnic minority populations. Health educators and public health professionals should consider generating awareness campaigns and partnering with community based organizations to disseminate proper knowledge. In addition, resources and awareness campaigns should be culturally tailored and linguistically appropriate to meet the needs of all racial and ethnic groups.

Citation Format: Dayanara Ruiz. A needs assessment of genetic and hereditary breast cancer awareness in Southern California women diagnosed with a genetic mutation [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B111.
Abstract B125: A culture of belonging in the pursuit of inclusive excellence
Authors: Nelson Joni , Shungu Nicholas , Harley Destiny
Published: September 2024

Significance: Over the past two decades, fostering diversity in the clinical and biomedical workforce has emerged as a best practice for improving cancer health outcomes and reducing cancer inequities. Cultivating a culture of belonging is a pivotal strategy for recruiting and retaining a diverse cancer workforce, particularly for individuals from underrepresented backgrounds. The Hollings Cancer Center (HCC) at the Medical University of South Carolina maintains a strategic aim to recruit, train, and develop a cancer workforce that reflects the diversity of the catchment area. In alignment with this aim, the HCC Office of Programs to Enhance Diversity (OPED) led a two-part forum that prioritized strategies to promote a culture of belonging. The forum included 1) a nationally renowned keynote speaker who detailed the significance of a culture of belonging and its intersections with recruitment and retention of a diverse cancer workforce and 2) table-top discussion with forum attendees intended to identify actionable initiatives that foster a culture of belonging. Methods: We utilized a quality improvement approach to explore opportunities to advance a culture of belonging within the HCC infrastructure. To assess the impact of the forum we conducted a descriptive analysis on attendee feedback surveys and thematic analysis of table-top discussions. Results: 34 forum attendees completed the evaluation survey. 97% of respondents felt that the forum was a good use of their time and 85% of respondents reported the information presented in the forum helped them reflect on their own sense of belonging. Two primary themes emerged from the table-top discussions: the pursuit of systematic approaches for fostering inclusivity and ensuring feasible pathways for diverse recruitment and retention. Additionally, the forum was a critical strategy for yielding key recommendations from attendees regarding actionable steps needed to foster a culture of belonging (e.g. use of welcome videos, mechanisms for addressing microaggressions, targeted recruitment advertisements, and establishment of affinity groups). Conclusion: In this presentation, we will delineate strategic pathways forward for the ongoing cultivation of a culture of belonging in the pursuit of inclusive excellence within the cancer workforce.

Citation Format: Joni Nelson, Nicholas Shungu, Destiny Harley. A culture of belonging in the pursuit of inclusive excellence [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B125.
Abstract B145: County-level food insecurity and hepatocellular carcinoma risk: A cross-sectional analysis
Authors: Kehm Rebecca D. , Vilfranc Chrystelle L. , McDonald Jasmine A. , Wu Hui Chen
Published: September 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR002) of the Conference Program/Proceedings.

Citation Format: Rebecca D. Kehm, Chrystelle L. Vilfranc, Jasmine A. McDonald, Hui Chen Wu. County-level food insecurity and hepatocellular carcinoma risk: A cross-sectional analysis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B145.
Abstract B153: Social and Structural Influences of Preventive Cancer Screenings for Native Hawaiian and Pacific Islander Adults in Hawaiʻi
Authors: Willingham Mark L. , Cassel Kevin , Zhang Wei , Diaz Tressa P. , Sy Angela , Pagano Ian , Ta'afaki Munirih R. , Mummert Angelina G.
Published: September 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR012) of the Conference Program/Proceedings.

Citation Format: Mark L. Willingham Jr., Kevin Cassel, Wei Zhang, Tressa P. Diaz, Angela Sy, Ian Pagano, Munirih R. Ta'afaki, Angelina G. Mummert. Social and Structural Influences of Preventive Cancer Screenings for Native Hawaiian and Pacific Islander Adults in Hawaiʻi [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B153.
Abstract B177: Association between ethnicity and ovarian cancer tumor characteristics in Asian Americans in California
Authors: Lee Alice W. , Chang Jenny , Siddiqui Sannia , Ziogas Argyrios , Bristow Robert E.
Published: September 2024

Background: Ovarian cancer is often associated with poor survival given that most patients are diagnosed at advanced stages when treatment is less effective. The disease is also very heterogeneous, consisting of various histologic subtypes that each have distinct epidemiologic and pathologic profiles. Given that some studies have noted ethnic-specific disparities in ovarian cancer survival when the Asian American population is disaggregated and certain tumor characteristics are associated with more favorable outcomes, we examined the relationship between Asian ethnic subgroup and ovarian cancer disease presentation. Methods: We included a total of 31,230 non-Hispanic White and Asian/Pacific Islander ovarian cancer cases diagnosed between 1996 and 2020 from the California Cancer Registry. Multivariable logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) was used to examine the likelihood of being diagnosed with tumors of a certain stage, grade, and histologic subtype, for each Asian ethnic subgroup compared to non-Hispanic Whites. Demographic and socioeconomic factors were considered in the analyses. Results: Most, but not all, Asian ethnic subgroups were less likely to be diagnosed with advanced stage ovarian cancer and more likely to be diagnosed with clear cell ovarian cancer compared to non-Hispanic Whites. For South East Asians, the odds of having advanced stage tumors were 43% lower than non-Hispanic Whites (OR=0.57, 95% CI 0.41-0.79) and the odds of having clear cell tumors were almost 200% higher than non-Hispanic Whites (OR=2.97, 95% CI 1.92-4.61); only South Asians did not show lower odds of an advanced stage tumor diagnosis (OR=1.06, 95% CI 0.86-1.29) and higher odds of a clear cell tumor diagnosis (OR=0.93, 95% CI 0.63-1.37). Conclusion: There are clear differences in ovarian cancer disease presentation when each Asian ethnic subgroup is examined separately with South Asians constituting the only subgroup who did not show a lower likelihood of an advanced stage diagnosis and a higher likelihood of a clear cell diagnosis when compared to non-Hispanic Whites. Given that tumor stage and histologic subtype are considered important prognostic factors for ovarian cancer, identifying the underlying factors that may contribute to being diagnosed with certain tumor characteristics could provide clues to help us improve the survival of this highly fatal malignancy.

Citation Format: Alice W. Lee, Jenny Chang, Sannia Siddiqui, Argyrios Ziogas, Robert E. Bristow. Association between ethnicity and ovarian cancer tumor characteristics in Asian Americans in California [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B177.
Abstract B178: Examining ovarian cancer survival by Asian American ethnic subgroup: An analysis of California Cancer Registry data
Authors: Lee Alice W. , Chang Jenny , Siddiqui Sannia , Ziogas Argyrios , Bristow Robert E.
Published: September 2024

Background: Ovarian cancer is the leading cause of death among gynecologic malignancies. However, outcomes are not the same for all women with studies showing Asian Americans having the highest survival across all major racial groups. Since the Asian American population is heterogeneous, we examined ovarian cancer survival by Asian ethnic subgroup using data from the California Cancer Registry. Most ovarian cancer survival studies evaluate Asian Americans as a single aggregated group, which may mask important ethnic-specific disparities. Methods: A total of 31,230 ovarian cancers diagnosed among non-Hispanic Whites and Asian/Pacific Islanders between 1996 and 2020 were included in the analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the risk of dying from ovarian cancer comparing the Asian ethnic subgroups to non-Hispanic Whites using Cox proportional hazards models. The survival analyses also considered demographic, tumor, socioeconomic, and treatment characteristics. Results: For most Asian ethnic subgroups, risk of dying from ovarian cancer was comparable to non-Hispanic Whites with the only exception being Other Asians who showed a statistically significant 15% decreased risk of ovarian cancer death (HR=0.85, 95% CI 0.73-0.97, p-value=0.02). Another notable finding was the increased risk of death observed among Pacific Islander ovarian cancer patients when compared to non-Hispanic White patients (HR=1.27, 95% CI 0.99-1.62, p-value=0.06). Conclusion: Although most studies show Asian Americans having the highest ovarian cancer survival, our analyses indicate that only Other Asians have better survival and Pacific Islanders may have poorer survival relative to non-Hispanic Whites, highlighting the importance of disaggregation in future studies. These ethnic-specific disparities that were observed even after accounting for relevant survival-related characteristics should be further explored as it may inform important biological and behavioral factors associated with survival, which are not captured in cancer registry data.

Citation Format: Alice W. Lee, Jenny Chang, Sannia Siddiqui, Argyrios Ziogas, Robert E. Bristow. Examining ovarian cancer survival by Asian American ethnic subgroup: An analysis of California Cancer Registry data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B178.
Abstract C015: Unraveling the structure of the Philadelphia chromosome using super-resolution microscopy
Authors: Dewson Gabrielle S. , Nir Guy
Published: September 2024

Philadelphia-positive leukemia is characterized by the translocation t(9;22)(q34;q11), which results in the oncogene BCR-ABL1 and a chromosome called the Philadelphia (Ph) chromosome (chr). The Philadelphia chromosome is best characterized in Chronic Myeloid Leukemia (CML); however, the translocation is also found in Acute Lymphoblastic Leukemia (ALL). Philadelphia-positive ALL has been historically understudied, especially in minority populations. Genome organization is a highly complex process by which chromatin is segregated within the nucleus into specific domains, making stable translocations highly unfavorable. How translocations are stabilized has been historically understudied. Here, we aim to examine how the Ph chr is stabilized and be the first to visualize an entire abnormal chr with high spatial and genomic resolution at the single-cell level. Using OligoSTORM, a super-resolution microscopy technique, we aim to image the entirety of the Ph chr at a nanoscale resolution in both CML and ALL cell lines. In addition to the DNA super-resolution trace, we have designed an RNA library to image a series of RNAs from the Ph chr on the same sample as the DNA trace, allowing us to connect the transcriptional data to the chromatin structure. We have successfully traced the entirety of the Ph chr. We have preliminary data suggesting that chr9 and chr22 segregate close to each other in non-leukemia healthy cells. We have also proven that our library design and methodology work to achieve the primary 500kb resolution. Preliminary data suggests that chr9 and chr22 in cells, that don’t typically have a Ph chr, segregate within proximity to translocate successfully. This study aims to compare the 3D structure of CML, ALL and non-leukemia cell lines to potentially identify genome organization-based biomarkers for identify and targeting the Philadelphia chromosome.

Citation Format: Gabrielle S. Dewson, Guy Nir. Unraveling the structure of the Philadelphia chromosome using super-resolution microscopy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C015.
Abstract C016: Optical Techniques to Democratize Intravital Quantification of Metabolic Heterogeneity
Authors: Sunassee Enakshi
Published: September 2024

Since metabolic and vascular adaptations are essential for tumor cell survival, a technique capable of tracking metabolic heterogeneity at both the bulk tumor and cellular scales over extended timelines is necessary. To address this technological need, we have developed a multi-scale optical microscope relying on exogenous fluorescent reporters for dynamic spatiotemporal imaging of major metabolic pathways in vivo. This microscope utilizes a low-cost CMOS detector and LEDs for excitation to enable fluorescence microscopy in resource-limited settings. Here, we implement our system to assess changes in bulk tumor and cellular metabolic heterogeneity as vasculature is perturbed. 4T1 breast tumor-bearing mice were treated with combretastatin A-1 (a vascular disruptor), implanted with window chambers, and temporally imaged (n=5/group). Fluorescence imaging and Gabor filter/Djikstra segmentation approaches enabled metabolic and vascular analyses, respectively. We demonstrated the system’s ability to acquire co-registered images of vasculature, morphology, and distinct metabolic endpoints reporting on glucose uptake, fatty acid uptake, and mitochondrial metabolism at both wide-field and high resolutions. At 12 hours post-treatment, the tumors’ metabolism shifted from mitochondrial respiration to glycolysis in avascular regions. Further, we report a higher average vascular density in untreated versus treated mice at 108 hours post-treatment (p<0.05, Kolmogorov-Smirnov test). On exploring the relationship between metabolic activity and vasculature, regions with high local tortuosity in the untreated group exhibited a higher reliance on fatty acid uptake than high tortuosity regions in the treatment group, indicating these cells’ reliance on fatty acids within a complex vascular network. Our multiplexed imaging strategy enables the quantification of tumor metabolism and vasculature over multiple length scales, which could be leveraged to study adaptations following clinical therapies.

Citation Format: Enakshi Sunassee. Optical Techniques to Democratize Intravital Quantification of Metabolic Heterogeneity [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C016.
Abstract C028: Effects of co-treatment with polyisoprenylated cysteinyl amide inhibitors and sotorasib on cell viability and ras signaling pathways in an African American lung cancer cell line
Authors: Mensah-Mamfo Justin K. , Ofosu-Asante Kweku
Published: September 2024

Lung adenocarcinoma (LUAD) is the most prevalent type of lung cancer among Blacks/African Americans(B/AAs) and all other racial and ethnic groups. Therapies that directly target mutant KRAS, the most common driver of LUAD, have been difficult to develop. Anti-cancer drugs such as Sotorasib, a KRASG12C inhibitor, were developed to treat cancers driven by the mutant KRAS protein. Nevertheless, recent studies have highlighted the limitations of Sotorasib as a viable long-term treatment due to intrinsic changes in cells, resulting in resistance and relapse. Polyisoprenylated Cysteinyl Amide Inhibitors (PCAIs) are novel anti-cancer agents developed to target hyperactive G-proteins such as KRAS, RHOA, CDC42 and RAC1 by disrupting their polyisoprenylation-dependent interactions. Previous work, using lung adenocarcinoma cell lines NCI-H23, derived from a B/AA male patient, revealed that PCAIs induce apoptosis in cells while inhibiting cell migration and invasion by 82%. Furthermore, the PCAI treatment induced hyperphosphorylation of the MAP kinase proteins MEK1/2, ERK1/2, p90RSK and AKT in the PI3K/AKT pathway. Current experiments seek to explore the effects of co-treatment with PCAIs and Sotorasib on cell viability and phosphorylation of MAP kinase proteins. Cell viability studies indicate increased potency when cells are co-treated with PCAIs and Sotorasib compared to treatments with individual compounds. The EC50 obtained for individual treatments of PCAI NSL-AB-51 and Sotorasib were 2.7 mM and 19 mM, respectively. The EC50 obtained for the treatments with varying concentrations of NSL-AB-51 combined with 18 mM Sotorasib, and varying concentrations of Sotorasib combined with 2.7 mM NSL-AB-51 were 1.8 mM and 10 mM, respectively. Preliminary western blot data indicates that the PCAIs induce the hyperphosphorylation of the MAP kinase pathway kinases MEK1/2, ERK1/2, and p90RSK. However, introduction of Sotorasib reverses the PCAI-induced hyperphosphorylation. Ongoing work is aimed at elucidating the interplay between PCAIs and Sotorasib with respect to cell viability and growth signaling pathway activations using cell lines with different KRAS mutations.

Citation Format: Justin K. Mensah-Mamfo, Kweku Ofosu-Asante. Effects of co-treatment with polyisoprenylated cysteinyl amide inhibitors and sotorasib on cell viability and ras signaling pathways in an African American lung cancer cell line [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C028.
Abstract C030: The Wip1 phosphatase activator QGC-8-52 selectively sensitizes p53-deficient cancer cells to chemotherapy
Authors: Wu Ke , Wu Yong , Vadgama Jay , Chen Qiao-Hong , Huang Zhi-min , Li Qun
Published: September 2024

PP2C serine-threonine phosphatase Wip1 is vital for tissue homeostasis, stress signaling, and the pathogenesis of various diseases, making it a promising target for cancer therapy. Inhibiting Wip1's expression or activity is a novel strategy to prevent cancer. However, traditional Wip1 suppression may not work in cancers lacking p53. Here, we evaluated a new Wip1 activator, QGC-8-52, in preclinical breast cancer models. QGC-8-52 sensitizes p53-deficient cancer cells to chemotherapy by facilitating Wip1-FOXO3a interaction and dephosphorylation of Thr487, which enhances FOXO3a's activity on the proapoptotic TRAIL gene. This effect is specific to p53-deficient cancer cells. In normal cells, Wip1 activation reduces drug-induced apoptosis by weakening upstream signaling to p53. Thus, activating Wip1 during chemotherapy boosts apoptosis in p53-negative tumors and protects normal tissues. Our findings highlight Wip1 activation as a potentially effective and safe treatment for p53-deficient cancers.

Citation Format: Ke Wu, Yong Wu, Jay Vadgama, Qiao-Hong Chen, Zhi-min Huang, Qun Li. The Wip1 phosphatase activator QGC-8-52 selectively sensitizes p53-deficient cancer cells to chemotherapy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C030.
Abstract C039: Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study
Authors: Kroenke Candyce , Aoki Rhonda , Alexeeff Stacey , Gomez Scarlett , Caan Bette , Morey Brittany , Torres Jacqueline , Kushi Larry
Published: September 2024

Background: Associations of nativity and breast cancer (BC) mortality are mixed in studies using cancer registry data. We examined associations in diverse women with detailed individual-level data on BC treatment and subtype. Methods: The study population included 5,718 Asian (n=722, 71% foreign-born), Hispanic (n=631, 42% foreign-born), and non-Hispanic White (n=4,365, 9% foreign-born) women from the ENCLAVE Study diagnosed with invasive BC from 1996-2013 using pooled, harmonized data from two (of three) cohorts with data on BC subtype. Data on nativity, reproductive and behavioral factors were self-reported from questionnaires; data on disease severity, BC subtype (luminal A, luminal B, Her2 expressing, triple negative breast cancer), treatment, and mortality were obtained from cancer registries and electronic health records. Recurrences were identified by recurrence algorithms and medical record review. We fit Cox proportional hazards regression models to examine associations between self-reported nativity and recurrence, BC-specific mortality, and overall mortality. Covariates included age, sociodemographic factors, disease severity, and treatment, reproductive and behavioral factors. We also examined associations by race, ethnicity, and BC subtype. Results: Compared to US-born women, foreign-born women had lower total mortality (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.64-0.89); lower risks were suggested for recurrence (HR=0.85, 95% CI: 0.68-1.06) and breast cancer-specific mortality (HR=0.87, 95% CI: 0.66-1.14). Stratified by BC subtype, foreign- (vs. US-) born women had a lower risk of overall mortality among those with luminal A (HR=0.72, 95% CI: 0.56-0.92) and luminal B (HR=0.66, 95% CI: 0.48-0.91) but not other subtypes. Among women with luminal B BC, these associations reached statistical significance for recurrence (HR=0.65, 95% CI: 0.45-0.94) and BC-specific mortality (HR=0.53, 95% CI: 0.33-0.84). We noted no associations in other BC subtypes though analyses of less common subtypes were underpowered. Associations did not differ by race or ethnicity. Conclusion: Foreign-born women with BC had lower risk of overall mortality than US-born women. Risks of recurrence and BC-specific mortality were lower in foreign-born vs. US-born women among those with the luminal B BC subtype. Associations were not explained by behavioral or reproductive factors.

Citation Format: Candyce Kroenke, Rhonda Aoki, Stacey Alexeeff, Scarlett Gomez, Bette Caan, Brittany Morey, Jacqueline Torres, Larry Kushi. Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C039.
Abstract C041: A systematic review of cardiovascular health among cancer survivors
Authors: Miles Miriam A. , Anderson-Tolbert Le’Andrea , Ninson Abigail A. , Means Cha-Breia , Smith Tuchondriana , Coleman Reagan , Rogers Laura , Joseph Joshua , Nolan Timiya S.
Published: September 2024

Purpose: The most common non-cancer cause of death among cancer survivors is cardiovascular disease. Health behaviors (e.g., diet, physical activity, sleep, smoking) and health factors (e.g., blood pressure, hemoglobin A1C, cholesterol) associated with cancer mortality are also associated with cardiovascular mortality. The American Heart Association has termed these behaviors and factors “cardiovascular health” (CVH) or “Life’s Essential 8,” providing a metric to determine poor, intermediate, and high (ideal) CVH. Less than ideal CVH is associated with higher cancer mortality; however, little is known about the CVH of cancer survivors. The purpose of this systematic review is to examine the extant literature on CVH among cancer survivors. MethodsIn accordance with PRISMA guidelines, we are systematically examining cardiovascular health among cancer survivors (including patients) within PubMed, Scopus, CINAHL, and Embase databases without date limitations. Two reviewers are accessing articles at each level of review to determine concordance with inclusion criteria, coming to consensus via a shared discussion. Data from studies that meet inclusion criteria will be abstracted, assessed for risk of bias. and synthesized to understand themes of CVH among cancer survivors. Results To date, we have retrieved 1,990 studies from the named databases. Preliminary review of the title and abstracts suggests that CVH as a metric may be seldom used within extant literature. This review is ongoing. Conclusion: Given the co-morbid and iatrogenic nature of cardiovascular disease among cancer survivors, it is important to understand metrics that can be applied to both identify cancer survivors with increased risk of poor outcomes and educate/empower cancer survivors to make modifiable changes to reduce their risk. This review will provide much needed evidence to support future research, practice changes, and policy implications to support the long-term health of cancer survivors.

Citation Format: Miriam A. Miles, Le’Andrea Anderson-Tolbert, Abigail A. Ninson, Cha-Breia Means, Tuchondriana Smith, Reagan Coleman, Laura Rogers, Joshua Joseph, Timiya S. Nolan. A systematic review of cardiovascular health among cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C041.
Abstract C056: Improving Adherence to Cancer Care in Underserved Patients with Central Nervous System Tumors through the Integrated Cancer Care Access Network (ICCAN)
Authors: Elshiekh Cleopatra , Phillips Ashley , Rodriguez Ashley , Narang Bharat , Gany Francesca , Budhu Joshua
Published: September 2024

This pilot study investigates the impact of the Integrated Cancer Care Access Network (ICCAN) on treatment adherence for patients with central nervous system (CNS) tumors. Patients with CNS tumors often face significant financial toxicity due to a lack of ability to work, physical disabilities due to their disease, and cognitive changes due to treatment and disease. Patients were enrolled in the ICCAN intervention, a longstanding multidisciplinary patient navigation and socioeconomic resources facilitation program, where an initial essential needs survey was administered. The survey consisted of questions regarding food security, housing circumstances, monthly individual and household income, and transportation barriers that patients were facing. If patients could not complete the survey independently due to their disease, a caregiver helped answer the survey questions. The clinical research coordinator helped procure appropriate resources based on the needs expressed. Patient navigation services were also provided to facilitate patient engagement and adherence to treatment and appointments. Patients were provided access to the Memorial Sloan Kettering food pantry, gift card services, assistance applying for grants, and transportation assistance. Patients were followed at 2 months, 4 months, 6 months, and 12 months post the initial essential needs survey. Overall, the largest needs for the CNS tumor patients enrolled in ICCAN were housing, income due to lack of ability to work, food insecurity, and transportation barriers for appointments. Many patients expressed gratitude for the services provided and consistently followed up with the clinical research coordinator regarding any apparent new needs. There is a lack of research on the financial toxicity of patients with CNS tumors, and this pilot program provided proof of concept that patients with CNS tumors can be successfully enrolled in a patient navigation and resources intervention. Based on this data, we will expand this intervention into a randomized clinical trial.

Citation Format: Cleopatra Elshiekh, Ashley Phillips, Ashley Rodriguez, Bharat Narang, Francesca Gany, Joshua Budhu. Improving Adherence to Cancer Care in Underserved Patients with Central Nervous System Tumors through the Integrated Cancer Care Access Network (ICCAN) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C056.
Abstract C072: Evaluating the use of vincristine as a substitute for vinblastine in Hodgkin lymphoma treatment
Authors: Sarhan Zaid , Atmeh Mousa , Al-Saudi Mohammad , AlFattah AlNsour Abed , Alghafri Osama , AlDin Sarhan Dia’a , Al-Dalaeen Raneem
Published: September 2024

Introduction: Classical Hodgkin lymphoma (HL) is a type of cancer originating from B lymphocytes, characterized by a high annual incidence globally. While the ABVD regimen (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine) is the standard treatment, this study explores substituting Vinblastine with Vincristine (ABOD regimen) to potentially enhance efficacy and treatment outcomes. Purpose: The primary aim was to evaluate the efficacy of the ABOD regimen compared to the ABVD regimen in treating classical Hodgkin lymphoma. The study also aimed to identify factors influencing treatment response, relapse risk, and the indication for alternative treatments such as escalation therapy, salvage therapy, immunotherapy, and transplantation. Method: This retrospective study reviewed 83 patients diagnosed with classical HL and treated at the Military Cancer Center in Jordan from January 1, 2017, to February 1, 2023. Data on demographics, disease characteristics, treatment regimens, and outcomes were collected and analyzed using logistic regression and Chi-square tests to evaluate associations between variables and treatment outcomes. Results: The study included 83 patients, with a mean age of 35.67 years, and a predominance of females (60.24%). The most common subtype was nodular sclerosis (84.34%), with stage 4 disease being the most prevalent (45.12%). Treatment response after the second cycle of ABOD was significantly better in older patients. There was no significant association between bulky disease and treatment response or relapse risk. Younger patients required dose escalation more frequently, suggesting the ABOD regimen might be more suitable for older patients. Gender, histological subtype, and disease stage were not significantly associated with treatment response or relapse risk. Conclusion: The ABOD regimen, using vincristine instead of vinblastine, presents a viable alternative to the ABVD regimen for classical Hodgkin lymphoma treatment, particularly benefiting older patients due to favorable response rates and manageable toxicity. The findings highlight the need for further research to optimize treatment strategies for different patient subgroups and confirm the benefits of the ABOD regimen.

Citation Format: Zaid Sarhan, Mousa Atmeh, Mohammad Al-Saudi, Abed AlFattah AlNsour, Osama Alghafri, Dia’a AlDin Sarhan, Raneem Al-Dalaeen. Evaluating the use of vincristine as a substitute for vinblastine in Hodgkin lymphoma treatment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C072.
Abstract C076: Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities
Authors: Rangel Valeria , Quintero-Rivera Fabiola , Tanjasiri Sora , Masri Selma , Fleischman Angela , Pannunzio Nicholas R.
Published: September 2024

Activation-induced cytidine deaminase (AID) is a B cell-specific mutator required for antibody diversification. However, it is also implicated in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain blood cancers is critical in assessing disease severity and treatment options. We have developed a digital PCR (dPCR) assay that allows us to quantify mutations resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs. Implementation of this new assay showed that increased AID levels in immature B cells increased genome instability at loci linked to chromosomal translocation formation. This included the CRLF2 locus that is often involved in translocations associated with a subtype of acute lymphoblastic leukemia (ALL) that disproportionately affects Hispanics, particularly those with Latin American ancestry. Using dPCR, we characterized the CRLF2 locus in B cell-derived genomic DNA from both Hispanic ALL patients and healthy Hispanic donors and found increased mutations in both, suggesting that vulnerability to DNA damage at CRLF2 may be driving this health disparity. Our ability to detect and quantify these mutations will potentiate future risk identification, early detection of cancers, and reduction of associated cancer health disparities.

Citation Format: Valeria Rangel, Fabiola Quintero-Rivera, Sora Tanjasiri, Selma Masri, Angela Fleischman, Nicholas R. Pannunzio. Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C076.