bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5162: TuFEst: a sensitive and cost-effective pan-cancer detection approach with accurate tumor fraction estimation
Authors: Lin Ziao , Stewart Chip , Martin Elizabeth E. , Danysh Brian P. , Jacobs Raquel A. , Slowik Kara , Lawton Lee , Lightbody Elizabeth , Rhrissorrakrai Kahn , Utro Filippo , Levovitz Chaya , Cibulskis Carrie , Ghobrial Irene M. , Shipp Margaret , Corcoran Ryan B. , Juric Dejan , Parida Laxmi , Parsons Heather A. , Getz Gad 
Published: June 2022

Abstract
Detecting cancer at early stages or upon recurrence is critical to decreasing cancer morbidity and mortality. We developed TuFEst (Tumor Fraction Estimator), a cost-effective computational approach for pan-cancer detection and tumor burden estimation from ultra-low coverage whole genome sequencing (~0.1x, ULP-WGS) of minimally invasive cell-free DNA (cfDNA). Current state-of-the-art methods estimate tumor fraction (TF) from ULP-WGS depending exclusively on total copy number variation, which loses tumor signal in either copy number-quiet tumors or tumors with copy-neutral loss-of-heterozygosity. Additionally, it is difficult in many cases to distinguish clonal from sub-clonal copy-number events, therefore complicating the ability to estimate tumor fraction. On the other hand, fragments shed into the blood from cancer cells, i.e., circulating tumor DNA (ctDNA), of various cancer types show significantly different length distribution than that from normal cells in healthy donors. By synergistically integrating both (i) copy number variation and (ii) altered fragment length signals, TuFEst successfully achieved higher sensitivity and more accurate TF estimation than current methods in &gt;200 cfDNA samples across different cancer types, even in low tumor-fraction cases (TF &lt; 0.1%). Application of TuFEst to serial cfDNA samples from blood biopsies demonstrate its utility in accurately estimating TF in ~100 cfDNAs, suggesting that TuFEst can be used to detect early cancer recurrence during different treatments. In one breast cancer patient receiving CDK4/6 therapy, TuFEst indicated disease progression 262 days earlier than routine imaging. Altogether, our work suggests that accurate TF estimation from cfDNA can not only aid in detecting cancer at early stages but also provide evidence of disease progression during treatment. We believe that such a non-invasive, cost-effective, pan-cancer detection method will benefit both initial cancer screening and monitoring of resistance to therapy in clinical applications.
Citation Format: Ziao Lin, Chip Stewart, Elizabeth E. Martin, Brian P. Danysh, Raquel A. Jacobs, Kara Slowik, Lee Lawton, Elizabeth Lightbody, Kahn Rhrissorrakrai, Filippo Utro, Chaya Levovitz, Carrie Cibulskis, Irene M. Ghobrial, Margaret Shipp, Ryan B. Corcoran, Dejan Juric, Laxmi Parida, Heather A. Parsons, Gad Getz. TuFEst: a sensitive and cost-effective pan-cancer detection approach with accurate tumor fraction estimation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5162.
Abstract 518: Association of CC chemokines with breast cancer disparity
Authors: Mir Hina , Brock Briana A. , Samant Rajeev , Singh Shailesh 
Published: June 2022

Abstract
Despite recent advances, breast cancer (BrCa) still affects many women, and the impact is disproportional in African Americans (AA) and European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting racial difference in BrCa biology. Our laboratory was the first to show the involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner, KMplotter, and antibody microarray, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, CCL7, CCL11, CCL17, CCL20, CCL22, and CCL25 in BrCa tissues. High mRNA levels of CCL7, CCL8, CCL17, CCL20, and CCL25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, CCL7, CLC8, CCL17, CCL20, and CCL25 was highest in TNBC. The expression of CCL11 and CCL22 was associated with HER2 expression. CCL7, CCL8, CCL17, CCL20, and CCL25 were elevated in AAs. Since CCL25 showed a significant association with decreased OS in AA, we examined the expression of CCR9, which is the only receptor for CCL25, and CCR9-mediated signaling in BrCa cell lines derived from AA and EA. Our data show higher expression of CCR9 in AA than EA and distinct molecular cascade in cells derived from AA than EA. Furthermore, higher CCR9 expressing cells showed poor response to Carboplatin upon CCR9 activation. In conclusion, our data suggest the association of distinct CC-chemokines in BrCa progression, OS, and disparate disease outcome in AA compared to EA patients implying CCR9 signaling to be a potential target for improving chemotherapeutic response.
Citation Format: Hina Mir, Briana A. Brock, Rajeev Samant, Shailesh Singh. Association of CC chemokines with breast cancer disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 518.
Abstract 5183: LGR5 CAR-T cells: A novel potential treatment against high grade serous ovarian cancer
Authors: Wang Wanqi , Bandara Veronika , Lokman Noor , Napoli Silvana , Gundsambuu Batjargal , Oehler Martin , Barry Simon C. , Ricciardelli Carmela 
Published: June 2022

Abstract
Ovarian cancer is second leading cause of cancer-related mortality among gynecological cancers in the Western world. Although initial responses to 1st line treatment is high, over 75% of patients eventually relapse and acquire chemotherapy resistance, which is the primary cause of ovarian cancer treatment failure. New therapies to improve patient outcome are therefore urgently required. Chimeric antigen receptor T (CAR-T) cell therapy is an adoptive immunotherapy that is currently being used to treat some blood cancers. CAR-T cell therapies have so far been less effective against solid cancers, due in part to the absence of suitable tumor-associated antigen (TAA).This study has investigated whether Leucine-rich repeat-containing G protein-coupled receptor 5, LGR5) is a suitable target for CAR-T cell therapy for ovarian cancer. We found that LGR5 is highly expressed in HGSOC cancer lines (COV318, COV362 and OAW28) and increased in HGSOC tissues following relapse with chemotherapy resistant disease. We assessed the cytotoxic effects of LGR5-CAR-T cells on a range of ovarian cancer cell lines and primary serous ovarian cancer cells derived from patient ascites in vitro by MTT and 3D spheroid assays. We demonstrated that LGR5-CAR-T cells were cytotoxic and significantly inhibited survival of ovarian cancer cell lines (COV318, COV362) that express high levels of LGR5 but not SKOV3 or OV90 that express lower LGR5 levels in monolayer culture. In addition, LGR5-CAR-T cells were cytotoxic and significantly inhibited survival of primary serous ovarian cancer cells compared to un-transduced CD3+ T cells. LGR5 CAR-T cells also exhibited anti-tumor activity against ovarian cancer cell lines (COV318, COV362 & OAW28) and primary serous ovarian cancer cells in vitro using 3D-spheroid culture assays. This study demonstrates that LGR5-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.
Citation Format: Wanqi Wang, Veronika Bandara, Noor Lokman, Silvana Napoli, Batjargal Gundsambuu, Martin Oehler, Simon C. Barry, Carmela Ricciardelli. LGR5 CAR-T cells: A novel potential treatment against high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5183.
Abstract 5193: Case report: Long-term response to Camrelizumab in a pretreated metastatic mixed testicular germ cell tumor patient
Authors: Zhang Hui , Jiang Da , Meng Erhong , Song Wenya , Zhang Xue 
Published: June 2022

Abstract
Introduction: To date, very limited information is available about the efficacy of immune checkpoint inhibitor (ICI) therapy in mixed testicular germ cell tumor (TGCT) or variations of DNA damage repair (DDR) genes as predicators for it.
Case presentation: We reported a 19-year-old male patient with pretreated metastatic mixed TGCT harboring 5 variations in the BRCA2, MSH6 and PMS2 genes detected using plasma-based circulating tumor DNA (ctDNA). He obtained a durable clinical benefit from single-agent Camrelizumab (a PD-1 inhibitor), with the progression-free survival (PFS) of over 19 months and overall survival (OS) of over 6 years.
Conclusion: To the best of our knowledge, this case is the first study of long-term benefit from ICI in a pretreated mixed metastatic TGCT patient harboring 5 variations of DDR genes detected using ctDNA.
Table 1. Genomic profile of the patient. Gene Transcript Exon Nucleotide change Alteration Mutant allele frequency/copy number (%) Sequencing depth (×) Medication guides CDH1 NM_004360 exon 15 c.2382delC p.V794fs 0.98 1018 Sensitive to bicalutamide FBXW7 NM_018315 exon 11 c.1761delG p.G587fs 1.88 1009 Sensitive to mTOR inhibitor BCR NM_004327 exon 19 c.3311C&gt;G p.A1104G 1.92 1148 BCR NM_004327 exon 19 c.3316G&gt;A p.D1106N 9.25 1124 BCR NM_004327 exon 22 c.3611C&gt;G p.A1204G 2.29 918 BCR NM_004327 exon 22 c.3615G&gt;A p.T1205T 2.05 926 BCR NM_004327 exon 22 c.3684T&gt;C p.P1228P 2.3 1000 BRAF NM_004333 exon 1 c.64G&gt;A p.D22N 54.15 301 BRCA2 NM_000059 exon 15 c.7522G&gt;A p.G2508S 49.21 1138 CDH1 NM_004360 exon 2 c.144A&gt;G p.R48R 0.7 1001 CYP2B6 NM_000767 exon 5 c.785A&gt;G p.K262R 35.63 595 FCGR3A NM_000569 exon 4 c.634T&gt;G p.F212V 99.75 810 FGFR1 NM_015850 exon 15 c.2017C&gt;T p.R673W 0.84 958 FGFR1 NM_015850 exon 15 c.1991G&gt;T p.W664L 0.25 815 LRIG3 NM_153377 exon 16 c.2589G&gt;A p.T863T 48.91 1143 MSH6 NM_000179 exon 10 c.4006G&gt;T p.V1336F 8.31 349 PMS2 NM_000535 exon 9 c.932A&gt;G p.H311R 0.27 1109 PMS2 NM_000535 exon 9 c.934A&gt;G p.M312V 0.44 1131 PMS2 NM_000535 exon 15 c.2570G&gt;C p.G857A 69.81 573 ROS1 NM_002944 exon 29 c.4783T&gt;C p.L1595L 50.62 1051 SMO NM_005631 exon 3 c.582A&gt;G p.E194E 48.98 1223 TSC2 NM_000548 exon 41 c.5209C&gt;A p.P1737T 1.04 866
Citation Format: Hui Zhang, Da Jiang, Erhong Meng, Wenya Song, Xue Zhang. Case report: Long-term response to Camrelizumab in a pretreated metastatic mixed testicular germ cell tumor patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5193.
Abstract 5223: Pediatric cancer incidence among racial/ethnic groups living in rural/urban areas of the United States
Authors: Shetty Priya B. , Lupo Philip J. , Scheurer Michael E. 
Published: June 2022

Abstract
Background: The impact of urban/rural residence on pediatric cancer incidence has not been well studied. Additionally, the impact of race/ethnicity on pediatric cancer incidence by urban/rural status has not been evaluated, which could inform our understanding of the roles of shared genetic and environmental causes of these malignancies.
Methods: Using SEER18, we calculated pediatric cancer incidences for individuals diagnosed 2000-2018 by residence (urban/rural). Next we calculated incidence rate ratios (IRR) to evaluate the role of race/ethnicity on incidence stratified by urban vs. rural status.
Results: See Table. Overall, most incidences were similar by residence, i.e., lower or equal in rural versus urban areas, except the rural group having significantly lower incidences of leukemias and germ cell tumors (GCTs). Additionally, the incidence of most pediatric cancers was consistently higher among NHW in both urban and rural areas. Yet, incidence of some cancers differed by urban/rural residence within race/ethnicity: retinoblastoma (NHB, Hispanic, and API); soft tissue sarcomas (NHB and AI/AN); hepatic tumors (AI/AN); and GCTs (API).
Conclusions: In general, Hispanic, NHB, and AI/AN populations have similar incidence of pediatric cancers in urban or rural areas. These groups have some shared bio-geographical ancestry, suggesting a possible effect of genetics on risk. Further, differences in incidence by urban/rural residence within race/ethnicity suggest a possible role of environment for some cancers. Interestingly, for GCTs, NHB had a lower IRR in urban and rural areas, but Hispanic populations had a significantly higher IRR. This finding, consistent with a recent study in adults, suggest that African ancestry may confer a protective effect on risk of GCTs. Further, the GCT effect sizes were more protective in the rural group for each race/ethnicity group, suggesting the possible role of environmental factors and interactions of environment with ancestry.
Pediatric cancer incidence by race/ethnicity group and urban/rural residence
Citation Format: Priya B. Shetty, Philip J. Lupo, Michael E. Scheurer. Pediatric cancer incidence among racial/ethnic groups living in rural/urban areas of the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5223.
Abstract 5233: Evolution of therapy resistance through acquired KRAS amplification in ROS1 fusion KRAS G12C double positive NSCLC
Authors: Priest Katherine , Le Anh , Aisner Dara , Gebregzabheir Amanuail , Nijmeh Hala , Mandell Melanie , Davies Kurtis , O'Donnell Emily , Doebele Robert C. , Bao Liming , Schenk Erin L. 
Published: June 2022

Abstract
Patients with metastatic non-small cell lung cancer (NSCLC) positive for a ROS proto-oncogene 1 (ROS1) fusion usually experience significant disease response and long-term control while on treatment with a ROS1 targeting tyrosine kinase inhibitor (TKI) but significant clinical heterogeneity exists. The presence of co-occurring genomic alterations likely contribute to this diversity in clinical outcomes. Here, we report on a patient with metastatic NSCLC with a ROS1 fusion and Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation detected at diagnosis who experienced a short duration of disease control on targeted therapy. The patient was initially treated with entrectinib, a ROS1 TKI, and, at progression, also received sotorasib, a small molecule inhibitor of KRAS G12C, in combination. Using specimens from therapeutically relevant time points including at diagnosis, at time of resistance to entrectinib, and at time of resistance to entrectinib and concurrent sotorasib, we performed broad next generation sequencing and FISH studies to detail the development of therapy resistance. Variant allele frequency of KRAS G12C was increased at each time point (3.2%, 74.2%, and 97%, respectively). A cell line was derived from the patient at time of progression on entrectinib therapy. In vitro testing of the cell line demonstrated increased TKI responsiveness when treated with entrectinib and sotorasib. Signaling pathway analysis of the cell line showed entrectinib inhibited phosphorylation of ROS1 and AKT, but not ERK. Sotorasib alone or in combination with entrectinib resulted in decreased phosphorylation of ERK. In vitro testing suggested efficacy with the combination of entrectinib and sotorasib. However, in clinical follow up the patient’s disease demonstrated progression on the combination, likely related to KRAS G12C amplification. This case supports the need for broad molecular profiling for potential therapeutic and prognostic information to personalize therapy in patients with metastatic NSCLC.
Citation Format: Katherine Priest, Anh Le, Dara Aisner, Amanuail Gebregzabheir, Hala Nijmeh, Melanie Mandell, Kurtis Davies, Emily O'Donnell, Robert C. Doebele, Liming Bao, Erin L. Schenk. Evolution of therapy resistance through acquired KRAS amplification in ROS1 fusion KRAS G12C double positive NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5233.
Abstract 5242: Rationally designing a radionuclide drug conjugate for heterogeneous genomically stable gastric cancer
Authors: Yang Le , Xu Rui , Guo Peng , Yi Heqing , Cheng Xiangdong 
Published: June 2022

Abstract
Background: Gastric cancer (GC) is one of common malignant tumors with a 5-year survival rate less than 10% for patients in advanced stages. Genomically stable gastric cancer (GSGC), featuring the worst prognosis of four subtypes of GC based on its molecular characteristics, receives limited benefits from recently approved HER2-targeted antibody drug conjugates (ADCs) due to the lack and heterogeneity of tumoral HER2 expression. Currently, radionuclide drug conjugates (RDCs) have attracted great attention in targeted therapy, owing to its unique advantages of radiation-associated direct DNA damages and relatively long radiation distances. These unique advantages enable RDCs to efficiently and broadly ablate both cancer cells and cancer-associated stromal cells in heterogeneous tumor microenvironment without being internalized by target cells, featuring a novel and more efficient “bystander killing” effect than linker-cleavable ADCs. Here, a RDC was developed by rationally screening GSGC-targeting antibodies and radionuclides for targeted treatment of GSGCs. Meanwhile, the “bystander killing” effect of the RDC will be quantitatively determined and compared with conventional linker-cleavable ADCs.
Results: First, ICAM1 was identified as a more preferable molecular target relatively to HER2 in human GSGCs via flow cytometric analyses. Next, a RDC was constructed by covalently conjugating anti-ICAM1 antibody with radionuclide 131I via indogen chemistry. 131I, the RDC warhead emitting β-particles with an emission range of approximately 0.8 mm, is a clinically-used radionuclide with FDA approval for treating several tumors. Then, the half maximum inhibitory concentrations (IC50s) of constructed 131I conjugated ICAM1 antibody (131I-ICAM1) was evaluated in human GSGC cell lines. Its inherent bystander killing effect was validated by measuring the viability of ICAM1 negative cells co-incubated with ICAM1 positive cells in the treatment of 131I-ICAM1, in comparison with ADC of the same target. Ultimately, the anti-tumor efficacy of 131I-ICAM1 was verified in heterogeneous GSGC models. Simultaneously, the histopathological damages to normal organs by 131I-ICAM1 was minimized by optimizing its dose.
Conclusions: In this study, we constructed a rationally designed 131I-ICAM1 by conjugating ICAM-1 antibody and clinical available radionuclide 131I and investigated the intrinsic bystander killing effect of this RDC in ablating heterogeneous GSGCs. Our research explored the potential of 131I-ICAM1 as a promising targeted therapeutic candidate for treating heterogeneous GSGCs.
Citation Format: Le Yang, Rui Xu, Peng Guo, Heqing Yi, Xiangdong Cheng. Rationally designing a radionuclide drug conjugate for heterogeneous genomically stable gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5242.
Abstract 5316: Risk of cognitive impairment associated with androgen deprivation therapy in prostate cancer
Authors: Verma Shiv , Shankar Eswar , Singh Viabhav , Gupta Sanjay 
Published: June 2022

Abstract
Androgen deprivation therapy (ADT) is a commonly used clinical treatment for non-metastatic and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment results in adverse side-effects in patients including depression, frailty, cognitive impairment and dementia. Studies have reported increased levels of pro-inflammatory cytokines and inflammatory markers in older cancer patients, however, the relationship between inflammatory biomarkers and the severity of cognition in prostate cancer patients under ADT has not been investigated. We sought to identify peripheral biomarkers that could provide links between the mental changes and major pathological mechanisms responsible for the development of cognition in these patients. For these studies, gene expression data (GSE69223) of 30 matched malignant and non-malignant prostate tissue samples from 15 prostate cancer patients receiving neoadjuvant antiandrogen therapy before prostatectomy, were compared in parallel with postmortem brain tissue samples of Parkinson's and Alzheimer patients as additional neurological diagnosis. IPA analysis was performed in the context of known biological response and regulatory networks. Fisher’s exact test for each network was converted to a score of −log10 (p-value). Further validation was performed in BT142-neural cells and M059K-glial cells by qRT-PCR with and without antiandrogen (enzalutamide) treatment. A total of 1952 DEGs were identified in postmortem brain tissue specimens, and 101 DEGs were identified in prostate cancer patients receiving ADT before surgery. IPA analysis revealed 33 commonly expressed genes with changes in cytokine-cytokine signaling network overlapped in both patient cohorts. Pathway analysis showed that IL17 signaling pathway, regulation of cytokine production and changes in T-cell subsets by IL-17A and IL-17F were overrepresented. Furthermore, lipopolysaccharide, tumor necrosis factor and toll-like receptors were identified as upstream transcriptional regulators of these signaling pathways. Gene expression of pro-inflammatory cytokines viz. LIFR, IL1RN, IL6, IL10 and LIF were increased in both neural and glial cells treated with enzalutamide, compared to non-enzalutamide treated cells. Our results suggest that changes in cytokine signaling under the influence of ADT in prostate cancer patients may linked with cognitive impairment presenting new areas for diagnostic and therapeutic development in combating brain deficits.
Citation Format: Shiv Verma, Eswar Shankar, Viabhav Singh, Sanjay Gupta. Risk of cognitive impairment associated with androgen deprivation therapy in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5316.