bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 774: Genetic architecture, evolutionary genomics, and genomic risk of prostate cancer in sub-Saharan Africa
Authors: Rebbeck Timothy R. , Janivara Rohini , Chen Wenlong C. , Hazra Ujani ,   MADCaP Network, Lachance Joseph 
Published: March 2024

Abstract
Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We performed the first large-scale genomic analysis of CaP across sub-Saharan Africa (SSA). We evaluated the evolutionary history of CaP-associated loci, generated a novel genomic risk score, inferred ancestry-specific genetic architectures, and fine-mapped disease associations using in 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda through the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Multiple lead SNPs were private alleles in SSA, a pattern arising from recent mutations and the out-of-Africa bottleneck. These SSA-specific alleles contribute to haplotypes with odds ratios for CaP above 2.4. The genetic architecture of CaP differs across SSA, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that SSA CaP associations are largely governed by neutral evolution, as opposed to natural selection. This finding is consistent with the late onset of this disease. Focusing on 2,502 age-matched cases and 2,222 non-cancer controls, we generated a novel genomic predictor of CaP. We then assessed the extent to which this polygenic risk score was correlated with age of onset, PSA levels, genetic ancestry, and family history of study participants. The performance of this novel polygenic risk score was tested on other populations of African descent, as well as populations with non-African ancestry. Our findings emphasize the utility of conducting genetic studies in diverse populations.
Citation Format: Timothy R. Rebbeck, Rohini Janivara, Wenlong C. Chen, Ujani Hazra, MADCaP Network, Joseph Lachance. Genetic architecture, evolutionary genomics, and genomic risk of prostate cancer in sub-Saharan Africa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 774.
Abstract 781: Impact of vitamin D and pyruvate carboxylase on hypoxia inducible lipid droplet associated (HILPDA) protein in metastatic breast cancer cells
Authors: Song Yazhen , Andolino Chaylen , Teegarden Dorothy 
Published: March 2024

Abstract
Metastatic breast cancer, a critical health issue for women globally, is closely linked to aberrant lipid metabolism. One feature of this dysregulated metabolism is the increase in lipid storage in the form of cytoplasmic lipid droplets (CLDs), although what drives their accumulation or their role in metastasis is not clear. In prior studies, we demonstrated that the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25(OH)2D) downregulates pyruvate carboxylase (PC), a key metabolic enzyme, thereby reducing lipid accumulation in metastatic breast cancer cells (MCF10CA1a). Additionally, we have demonstrated that both 1,25(OH)2D treatment and PC-inhibition reduce breast cancer cell migration. Therefore, the goal of the current research is to identify the proteins associated with CLDs in metastatic MCF10CA1a breast cancer cells following 1,25(OH)2D treatment or reduction in PC expression (shPC). Proteins from CLDs and whole cell lysates (WCL) were processed for untargeted proteomic analysis. In the CLD fractions, 1562 identified enriched proteins were common to both MCF10CA1a and 1,25(OH)2D treated cells, while 160 proteins were higher in the MCF10CA1a cells, and 550 proteins were higher in the 1,25(OH)2D-treated cells compared to MCF10CA1a CLD fraction. In the CLD fractions, MCF10CA1a and shPC cells had a similar level of 380 enriched proteins, although 65 were higher in the shPC compared with MCF10CA1a, whereas 1268 were more enriched in the MCF10CA1a CLD fraction. Hypoxia Inducible Lipid Droplet Associated (HILPDA, known to inhibit triacylglycerol lipolysis) was only enriched in the CLD fraction of the metastatic MCF10CA1a cells. HILPDA was not identified in the CLDs of the 1,25(OH)2D treated or the shPC cells, nor in any WCL fraction. Further investigation of HILPDA is important to determine if HILPDA plays a role in dysregulated cellular metabolism, including CLD accumulation, or migration, and may potentially be a target for future therapies to prevent breast cancer progression.
Citation Format: Yazhen Song, Chaylen Andolino, Dorothy Teegarden. Impact of vitamin D and pyruvate carboxylase on hypoxia inducible lipid droplet associated (HILPDA) protein in metastatic breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 781.
Abstract 812: Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women
Authors: Sudan Sarabjeet Kour , Sharma Amod , Vikramdeo Kunwar Somesh , Davis Wade , Nelson Cindy , Singh Karan , Singh Ajay Pratap , Singh Seema 
Published: March 2024

Abstract
Breast cancer (BC) continues to be the most common cancer and the second leading cause of cancer-related death in American women. Furthermore, it affects Black women more adversely than their White counterparts, who experience an early disease onset, diagnosed more often with aggressive triple-negative breast cancer (TNBC) molecular subtype, and face greater mortality. The reasons for these disparities; however, are largely unknown. Here, using a retrospective dataset, we examined the association of body mass index (BMI) with BC early onset and diagnosis with specific molecular subtype in race-based distributions. Study cohort included 1085 BC patients, who visited University of South Alabama Health clinics between October, 2017 and March, 2022. Patients were divided into three BMI [(normal weight, NW (&lt;24.9), overweight, OW (25-29.9), and obese, Ob (&gt;30.0)], three age (&lt;45 years, 45-65 years, &gt;65 years), and four molecular subtypes [Luminal A (HR+, HER2-), Luminal B (HR+, HER2+), HER2 enriched (HR-, HER2+), and TNBC (HR-, HER2-) categories. The data show a higher prevalence of BC in Ob women (46%) than OW (27%) and NW (27%) women of all age groups and its incidence was much greater in Ob Black women (61%) than Ob White women (39%). Further, Black women had nearly twice higher diagnosis at an early age than White women. Moreover, Ob Black women had over 7- and 1.5-folds higher incidence of early onset BC than NW and OW Black women, respectively, whereas, early onset BC did not exhibit a correlative pattern in White women. Luminal A and TNBC subtypes were the most common in women with early onset BC and Black women exhibited more than twice incidence of TNBC (32%) compared to the White women (14%) of all ages. In contrast, incidence of luminal A subtype was less prevalent in Black (57.4%) than in White (72.6%) women. Interestingly, both luminal A and TNBC subtypes were also more prevalent in Ob women; however, the risk of being diagnosed with TNBC increased dramatically in Ob Black women compared to Ob White women. Together, these findings establish obesity as a major underlying cause of early onset BC and TNBC diagnosis in Black women, which could be targeted to diminish the BC disparity gaps.
Citation Format: Sarabjeet Kour Sudan, Amod Sharma, Kunwar Somesh Vikramdeo, Wade Davis, Cindy Nelson, Karan Singh, Ajay Pratap Singh, Seema Singh. Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 812.
Abstract 821: Uptake of cervical cancer screening services by women living with HIV in Kajiado County Kenya
Authors: Kamau Caren , Njoroge Alice , Makokha Francis , Ashing Kimlin T. 
Published: March 2024

Abstract
Background: This project is an African Caribbean Cancer Consortium (AC3) facilitated study: Women living with HIV (WLHIV) are more susceptible to cancer due to their immune-compromised status. The Kenya Ministry of Health recommends that women diagnosed with HIV should be screened for cervical cancer annually by either visual inspection with acetic acid (VIA) or visual inspection with Lugol’s iodine (VILI), cytology and testing for HPV once every two years.
Objective: We determined the uptake of cervical cancer screening and HPV testing by women living with HIV (WLHIV) in Kajiado County in 2022.
Methodology: The electronic health information system was used to abstract data for WLHIV in Kajiado county. Kajiado county has 57 antiretroviral (ART) facilities. However, our analysis accessed data from 38 facilities whose data is captured in the health information system. Authorized health care workers from the county were requested to abstract redacted data from the health information system. No personal identifiers were collected from the system as a means of protecting the privacy of individuals and abiding with the Kenya’s data protection law. Authorization to access the county was obtained from the county’s department of health while ethical approval was obtained from Mount Kenya University’s Institutional Scientific and Ethics Review Committee.
Results: A total of 16,827 people living with HIV were enrolled for care at the 38 ART selected sites in 2022. Out on the total population that was enrolled for care, 11,785 (70%) were women with an age range of 15 to 49 years. A total of 3342 WLHIV, representing 28.36% of the target population, were screened by using visual inspection with acetic acid (VIA). Data for other methods of screening and HPV testing was not available in the health information systems. Of those screened, 3240 (97%) tested negative, 78 (2.3%) had positive results while 24 (0.7%) had suspicious lesions.
Conclusion: Our analysis shows low uptake of cervical cancer screening services with only 28.36% of the targeted women being screened in 2022. The only available testing method (VIA) is less robust as compared to cytology and HPV testing. We also found a gap in reporting of HPV testing in the county. We thus recommend implementation science research examining the systemic barriers to HPV testing and reporting to better inform best practice HPV-related cancer prevention and control policy and practice to reduce cancer-related morbidity and mortality among WLHIV.
Citation Format: Caren Kamau, Alice Njoroge, Francis Makokha, Kimlin T. Ashing. Uptake of cervical cancer screening services by women living with HIV in Kajiado County Kenya [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 821.
Abstract 871: Unveiling the potential of bispecific antibodies: A comprehensive analysis of efficiency, toxicity, and repurposing in cancer treatment
Authors: Wang Binbin , Madan Sanna , Schaffer Alejandro , Ruppin Eytan 
Published: March 2024

Abstract
Bispecific antibodies have emerged as promising candidates for cancer treatment, prompting the necessity for a comprehensive understanding of their potential efficacy and toxicity across various cancer types. Leveraging single cell sequencing data, we systematically evaluated the efficacy and toxicity of all cell surface gene pairs across multiple cancers. First, we found that gene pairs involved in successful bispecific antibodies phase I/II clinical trials exhibited significantly higher efficacy scores and lower toxicity scores than gene pairs in those that failed, underscoring the utility of our method in selecting high-quality bispecific pairs. Second, to facilitate the identification of new pairs, we established baseline efficacy and toxicity scores based on successful phase I/II clinical trials, employing these scores to assess the potential of novel combinations. We systematically identified both cancer type-specific and pan-cancer candidate new bispecific antibody pairs. This extensive analysis not only provides valuable insights into the potential of bispecific antibodies to broaden the spectrum of cancer treatments, but also yields a highly confident list of candidate gene pairs capable of constructing effective bispecific antibodies.
Citation Format: Binbin Wang, Sanna Madan, Alejandro Schaffer, Eytan Ruppin. Unveiling the potential of bispecific antibodies: A comprehensive analysis of efficiency, toxicity, and repurposing in cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 871.
Abstract 890: Multimodal modeling of digitized histopathology slides improves risk stratification in hormone receptor-positive breast cancer patients
Authors: Boehm Kevin M. , Marra Antonio , Reis-Filho Jorge S. , Chandarlapaty Sarat , Pareja Fresia , Shah Sohrab P. 
Published: March 2024

Abstract
In early-stage hormone receptor-positive breast cancer, genomic risk scores identify patients who stand to benefit from up-front chemotherapy but introduce financial and logistical hurdles to care. We assembled a cohort of 5,244 patients with 11,671 corresponding whole-side images of breast tumors stained with hematoxylin and eosin. We developed a multimodal machine learning model to infer risk of distal metastatic recurrence from routine clinical data. Specifically, the model interprets text from the pathologist’s report using a large language model and uses self-supervised vision transformers to interpret the corresponding whole-slide image. Tensor fusion joins the modalities to infer Genomic Health’s Oncotype DX recurrence score. Inferred recurrence score from the multimodal model correlated with measured score with a concordance correlation coefficient of 0.64 (95% C.I. 0.59 - 0.69) in the withheld test set, compared to 0.55 (95% C.I. 0.49 - 0.61) and 0.56 (95% C.I. 0.52 - 0.60) for the linguistic and visual unimodal models, respectively. The multimodal model attains an area under the precision-recall curve (AUPRC) of 0.69 (AUROC=0.88) for identifying high-risk disease in the full-information setting (when images and pathology reports with quantitative hormone receptor status and grade are available) in a withheld test set, compared to AUPRC of 0.61 and 0.66 for the linguistic and visual models, respectively. By comparison, in the same full-information setting, the clinical nomogram introduced by Orucevic et al. in 2019 achieves an AUPRC of 0.48. We suggest the operating point at which precision is 94.4% and recall is 33.3%. Digitized whole-slide images of routine breast biopsies and their associated synoptic pathology reports contain much of the information necessary to stratify patients by risk of distal metastatic recurrence, when modeled appropriately. Our model could enable hospitals to rapidly triage the need for genomic risk testing, possibly precluding one third of orders without loss of accuracy. This helps allocate scarce resources for genomic tests and valuable weeks prior to beginning therapy while maintaining the standard of precision oncology.
Citation Format: Kevin M. Boehm, Antonio Marra, Jorge S. Reis-Filho, Sarat Chandarlapaty, Fresia Pareja, Sohrab P. Shah. Multimodal modeling of digitized histopathology slides improves risk stratification in hormone receptor-positive breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 890.
Abstract 891: Turning data into information: Using PD3D® models to guide colorectal cancer therapy by Optim.AITM
Authors: Pfohl Ulrike , Mohd Abdul Rashid Masturah , Lim Jhin Jieh , Loskutov Juergen , Wedeken Lena , Chow Edward Kai-Hua , Saavedra Hugo , Reinhard Christoph , Regenbrecht Christian R. 
Published: March 2024

Abstract
Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies globally with up to 50 % of patients eventually progressing to metastatic disease. The mitogen-activated-protein kinase (MAPK) pathway emerges as a key player, being one of the most frequently mutated signaling pathways in the oncogenesis of CRC. However, given the numerous genomic aberrations and tumor heterogeneity in CRC, patients may benefit from combinatorial therapies, particularly those who have inoperable or metastatic tumors. In the present study, we investigated the feasibility of combining two platforms, patient-derived 3D (PD3D®) models with Optim.AI™, to identify more effective cancer therapies. PD3D® models can robustly retain the genotypic and histopathologic features of the primary patient tumor, model tumor heterogeneity and were shown to predict a patient’s drug response. Optim.AI™ is a hybrid computational-experimental platform that uses small data sets to rationally converge to optimal drug combinations within a defined drug search space. By mapping experimental data points to a second-order quadratic function, Optim.AI™ can predict every possible 531k data points and thus the cell-killing efficacy for all other possible combinations without testing each individual drug-dose combination. Two CRC PD3D® models with different mutation profiles were tested with 155 different combinations of 12 drugs at variant concentrations. The post-treatment cell viability was measured and used for Optim.AI™ analysis to evaluate and compare the best therapies. Optim.AI™ analysis revealed differential drug sensitivity between tested CRC PD3Ds®. The top-ranked drug combinations included SN-38, active compound of commonly used chemotherapeutic irinotecan, paired with MEK-inhibitors trametinib or cobimetinib which we could confirm with both platforms. With this study, we successfully demonstrated the feasibility, the robustness, and the efficiency of combining PD3Ds® and Optim.AI™ in identifying effective drug combination therapies, here for CRC, within one month. This combined technology provides precise insights into tumor treatability and its functional causes of treatment outcomes, leading to new treatment combinations and accelerating the development of new cancer drugs in a time- and cost-effective manner.
Citation Format: Ulrike Pfohl, Masturah Mohd Abdul Rashid, Jhin Jieh Lim, Juergen Loskutov, Lena Wedeken, Edward Kai-Hua Chow, Hugo Saavedra, Christoph Reinhard, Christian R. Regenbrecht. Turning data into information: Using PD3D® models to guide colorectal cancer therapy by Optim.AITM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 891.
Abstract 923: Biomarker use in oncology approvals in the US
Authors: Dou Yannan Nancy , Grimstein Christian , Wang Jian , Mascaro Jacques 
Published: March 2024

Abstract
Introduction: Precision medicine through the use of biomarkers has revolutionized the way we understand and combat cancer. We are summarizing the current state and challenges of biomarker use in the context of cancer therapeutic products approved by the United States Food and Drug Administration (FDA).
Methods: We curated a dataset of oncology therapeutic products approved by the FDA through the regular and accelerated pathways from 2011 to 2022, based on publicly available FDA database, approval letters and reviews, prescribing information, publications, and clinicaltrial.gov.
Results: During the period of 2011 to 2022, the FDA granted 132 accelerated and 331 regular approvals for 80 and 144 oncology therapeutic products with 133 and 340 new indications, respectively. The percentage of approvals for a biomarker-defined population was higher in accelerated approvals in comparison to regular approvals (i.e., 51% vs. 39%). The five disease sites with the highest number of approved indications were leukemia, lung, non-Hodgkin lymphoma, breast, and skin. The vast majority of lung and breast cancer indications were approved in a biomarker-defined population through a range of different biomarkers. Overall, HER2-, EGFR-, BRAF-, HR-, and ALK-defined populations received the highest numbers of approvals. The most common biomarkers linked to the approval of a specific cancer type include Philadelphia chromosome for leukemia, EGFR/ALK for lung cancer, HER2/HR for breast cancer, BRAF for skin cancer, and BRCA for ovarian cancer. Multiple myeloma, kidney cancer, and Hodgkin lymphoma did not have any approval with a biomarker-defined population. Non-Hodgkin lymphoma had a large number of approvals, but the percentage approved for a biomarker-defined population was small. dMMR, MSI-H or dMMR, BRAF mutation, NTRK fusions, TMB H, and RET fusions are biomarkers linked to tissue-agnostic indications approved for solid tumors only through the accelerated pathway.
Conclusion: To the best our knowledge, the analysis represents the most comprehensive overview of the current landscape on integration of biomarker in oncology therapeutic products approved by the FDA through both the accelerated and regular pathways. Our analysis shows that the FDA has increasingly approved indications based on biomarkers, particularly through the accelerated approval pathway. Biomarkers are reshaping cancer therapy under an evolving regulatory landscape with a growing emphasis on precision medicine that promises continued progress in personalized cancer care.
Citation Format: Yannan Nancy Dou, Christian Grimstein, Jian Wang, Jacques Mascaro. Biomarker use in oncology approvals in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 923.