bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization
Authors: Reitsamer Roland , Sir Andreas , Forsthuber Ernst , Peintinger Florentia
Published: May 2024

Background: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of SLNB alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NACT). However optimal methods for TAD are still under investigation. A paramagnetic marker Magseed® was used for the identification of the TLN in this study. Methods: 80 patients eligible to receive NACT were included. All patients had positive axillary lymph nodes verified by core biopsy. Six patients did not receive NACT for any reason. After NACT the targeted lymph nodes (TLNs) were marked with Magseed®, a non-radioactive paramagnetic marker. The SLNs were marked with dual tracer method. The SLNB and the selective TLNB were performed in 74 patients. The Magseed® marked TLNs were identified with the Sentimag® probe and excised. Specimen x-ray was performed to confirm the Magseed® within the prior to NACT biopsied and clipped lymph node. The identification rates of TLNs and SLNs, and the concordance rates were calculated. Results: The TLN identification rate was 100% (74/74), the SLN identification rate was 81.1% (60/74), the concordance rate of TLN and SLN was 58.1% (43/74). In 66.2% (49/74) of the patients the TLN converted to negative, and no ALND was performed. When the TLN converted to negative, a SLN could not be identified in 18.4% (9/49) of the patients. In 33.8% (25/74) of the patients the TLN remained positive after NACT and ALND was performed. When the TLN remained positive, a SLN could not be identified in 40% (10/25) of the patients. Complications according Magseed® deployment or identification could not be observed. Conclusion: Magseed® is a reliable and feasible marker for the identification of TLNs after NACT.

Citation Format: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger. Targeted Axillary Dissection with Paramagnetic Marker Localization [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-02.
Abstract PO5-24-09: Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model
Authors: Najafi A.
Published: May 2024

Despite rapid advancements in treatments and technology, breast cancer remains the second leading cause of cancer related morbidity in women in the US. As a heterogeneous disease, the unique genetic and phenotypic profile of each tumor complicates the prediction of treatment responses and optimized treatment strategies. One primary manifestation of phenotypic plasticity and concomitant intra-tumoral heterogeneity is the Epithelial-Mesenchymal Transition (EMT). The acquisition of migratory and invasive properties through EMT facilitates tumor metastasis and results in worse patient outcomes. As a result, the EMT and its reverse process (MET) often influence treatment response. However, the different mechanisms through which these therapeutic drugs affect the EMT-related phenotypic switching rates as well as each phenotype’s replication rates are unclear, and further investigation is required for better understanding their precise effect for directing optimal treatment strategies and improved patient outcomes. Here, we compile an atlas of publicly available metastatic and non-metastatic RNA sequencing data of breast cancer cell lines treated with therapeutic and chemotherapeutic drugs and propose a dual data-driven theoretical framework for understanding the effects of each drug on breast cancer treatment response. We infer the cell fractions, EMT phenotypic transition rates and phenotypic replication rates of each case through an extension of our previously developed hybrid data-driven and theoretical model, COMET. We infer single-cell RNA sequencing-derived EMT-related trajectories and apply a continuous time Markov chain model to infer inter-state transition rates. By analyzing the atlas of RNA sequencing data and integration with our framework, we gain novel insights into the context-specific mechanisms by which therapeutic drugs affect the phenotypic transition rates. This comprehensive understanding will contribute to optimizing breast cancer therapy and ultimately improving patient outcomes.

Citation Format: A. Najafi. Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-09.
Abstract PO5-25-05: Crosstalk between adipocyte and tumor cells with ESR1 mutations via adipsin enhances tumor growth
Authors: Belyakov Artem , Jin Kideok
Published: May 2024

While endocrine therapies have shown clinical benefits for breast cancer with ESR1 mutations, resistance development is a significant challenge. Evidence suggests that the complement system is critical to tumor development, and recent studies highlight the role of adipsin in breast cancer growth. In a previous study, we characterized the role of complement pathway-mediated adipsin in ESR1 mutant cell lines (Y537S and D538G), identifying the upregulation of adipsin, C3, and C3aR in ESR1 mutant cells. The interaction between C3a and C3aR enhanced ESR1 mutant cell growth, and inhibiting C3aR abolished cell growth and increased apoptosis. Combining C3aR inhibitors with fulvestrant or CDK4/6 inhibitors had a synergistic inhibitory effect on ESR1 mutant cells. Our findings suggest that the complement pathway plays a role in ESR1 mutant cell proliferation and that C3aR is a potential target to mitigate ESR1 mutant breast cancer growth and metastasis. Additionally, we demonstrated the critical role of the feedback loop of adipsin in ESR1 mutant cell growth in adipocyte crosstalk. Using differentiated mouse 3T3-L1 adipocytes induced with tumor-conditioned media from ESR1 mutant cells, we observed the upregulation of adipsin, C3, and C3a in the adipocyte secretome, which enhanced C3a levels. Blocking the interaction between C3a and C3aR in ESR1 mutant cells using a C3aR inhibitor significantly inhibited ESR1 mutant cell growth compared to wild-type cells and enhanced apoptosis. Our findings suggest that upregulation of adipsin from ESR1 mutant cells and adipocytes in crosstalk increases tumor cell growth. Future studies will investigate the critical role of adipsin's auto- and paracrine effects in breast cancer with ESR1 mutations.

Citation Format: Artem Belyakov, Kideok Jin. Crosstalk between adipocyte and tumor cells with ESR1 mutations via adipsin enhances tumor growth [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-05.
Abstract PO5-27-03: Mutational impact of APOBEC3A and APOBEC3B in a human cell line
Authors: Carpenter Michael , Temiz Nuri , Ibrahim Mahmoud , Jarvis Matthew , Brown Margaret , Argyris Prokopios , Brown William , Yee Douglas , Harris Reuben
Published: May 2024

A major source of mutation in cancer is DNA cytosine deamination by APOBEC3 enzymes resulting in C-to-T and C-to-G mutations in TCA and TCT motifs. Here, we develop a selectable system to quantify genomic mutations and compare the mutagenic activities of three leading APOBEC3 candidates - APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and nearly indistinguishable TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from TK mutant clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs over 70% of the time and APOBEC3B just under 50% of the time (Y=C/T; W=A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes are contributing in a combinatorial manner to the overall mutation landscape. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both enzymes.

Citation Format: Michael Carpenter, Nuri Temiz, Mahmoud Ibrahim, Matthew Jarvis, Margaret Brown, Prokopios Argyris, William Brown, Douglas Yee, Reuben Harris. Mutational impact of APOBEC3A and APOBEC3B in a human cell line [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-03.
Abstract PO5-27-08: Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells
Authors: Arreola David
Published: May 2024

In spite of a decreased rate of cancer onset, by about 33%, since 1991, it is still as dreadful and a major cause of death globally. After heart disease, cancer continues to be the second most prevalent cause of death in the US. According to the American Cancer Society, there will be around 2 million new cases of cancer identified in Americans in 2023, along with approximately 610,000 cancer-related deaths. Breast cancer will continue to be the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed and synthesized a multimode photothermal agent, FA-Hep-CuS, for the advancement of photothermal therapy of cancer. CuS nanoparticles deposited on heparin-conjugated folic acid (FA-Hep-CuS) were prepared by gently heating unfractionated heparin in dimethyl formamide (DMF), then adding N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC), and finally adding the aminated folic acid in DMF and stirring for four days. Further, FA-Hep was dispersed in DI water, then citrated CuS nanoparticles dispersed in DI water were added, and the mixture was stirred for 8 hours to prepare FA-Hep-CuS. Moreover, the activation of the nanoparticles by non-ionizing radiation (NIR; l= 808 nm) was also evaluated for increased anti-cancer efficiency. In MDA-MB-231 (Triple-negative or TNBC or ER⁻/PR⁻/Her2⁻) breast cancer cell lines, the cytotoxic effects of FA, CuS, and FA-Hep-CuS, as well as their ability to impede motility, have been investigated. They have also been examined to determine how they affect the expression of mesenchymal indicators and clonogenicity. All these demonstrated significant dose-dependent in-vitro cytotoxicity against MDA-MB- 231 breast cancer cells. The cell viability assay showed that the FA-CuS was more effective than FA and CuS. Activation of the nanoparticles with NIR resulted in the significantly enhanced dose-dependent inhibitory potential of the nanoparticles against the migratory properties of the aggressive TNBC cells. In agreement, the clonogenicity of the TNBC cells was also inhibited dose-dependently. We are now focusing on its inhibitory potential on the EMT markers of the TNBC cells. We further aim to investigate the effects of FA-Hep-CuS in in-vivo models of breast cancers.

Citation Format: David Arreola. Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-08.
Abstract PS10-08: Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting
Authors: Eriksson Mikael , Román Marta , Gräwingholt Axel , Heywang-Köbrunner Sylvia , Rossi Paolo , Hall Per
Published: May 2024

Background:

Image-derived AI risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across different screening settings and clinical feasibility.

Purpose:

To investigate the predictive performance of a clinically used image-derived AI-based breast cancer risk model in multiple European screening populations.

Methods:

Four European mammographic screening populations in three countries screened between 2009-2020 for women aged 45-69 was used to perform a nested case-control study. In total, 739 women with incident breast cancers were included together with 7,812 controls matched to cases on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) for risk assessment were extracted using AI from full-field digital mammograms. Breast cancer occurrence was assessed after two years of follow-up. Absolute risks of breast cancer were predicted using the risk model from negative mammograms at study-entry. Adjusted Area Under the receiver operating characteristic Curves (aAUC) estimated discriminatory performance and, adjusted risk-ratios estimated the stratification performance of women at high/general risk per the clinical guidelines.

Results:

The overall aAUC of the AI risk model was 0.72 (95%CI 0.70-0.75), range 0.71 (95%CI 0.67-0.75) to 0.74 (95%CI 0.69-0.78) for breast cancers developed in four screening populations. In the 4.6% of women classified at high risk using the NICE guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95%CI 5.6-8.0), compared with the 71% of women classified at general risk by the model. Similar risk-ratios were observed across tertiles of mammographic density. In the high-risk group, 22% of the 2-year future cancers were diagnosed, and 29% of stage 2 and higher cancers, p< 0.01.

Conclusions:

The AI risk model showed generalizable discriminatory performances across European populations and, captured ~30% of clinically relevant stage 2 and higher breast cancers in ~5% of high-risk women who were sent home with a negative mammogram. Similar results were seen in fatty and dense breasts. An image-derived AI model is feasible for personalized screening to improve screening outcomes.

Citation Format: Mikael Eriksson, Marta Román, Axel Gräwingholt, Sylvia Heywang-Köbrunner, Paolo Rossi, Per Hall. Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-08.
Abstract PS12-04: Inhibition of GPX4 enhances CDK4/6 inhibitor activity in breast cancer
Authors: Abreu Maria Teresa Herrera , Khalid Uzma , Ning Jian , Cutts Rosalind , Wilson Gemma , Lord Christopher , Swain Amanda , Turner Nicholas
Published: May 2024

Background:

Cyclin D-dependent kinases 4 and 6 (CDK4/6) inhibitors (CDK4/6i) including palbociclib, ribociclib and abemaciclib in combination with endocrine therapy are the standard of care for patients with estrogen receptor-positive (ER+). Despite the success of these treatments, cytostasis is frequently observed, and novel strategies that enhance efficacy are required to eradicate residual cancer in the clinic.

Methods:

In the search of an effective drug combinations to enhance the efficacy of CDK4/6 inhibitors in breast cancer, we performed a whole genome CRISPR-Cas9 suppressor screen in MCF-7, an ER+ model. We also carried out transcriptomics, proteomics, and functional molecular biology analysis of breast cancer models treated with palbociclib to identify resistant mechanisms.

Results:

The whole genome CRISPR-Cas9 screen revealed that multiple genes involved in oxidative stress and ferroptosis modulated palbociclib sensitivity, being GPX4 the top sensitizing hit. GPX4 is a key glutathione peroxidase that protects again ferroptosis by catalysing the reduction of phospholipid and cholesterol hydroperoxides. CRISPR-depletion or drug inhibition of GPX4 increased sensitivity to palbociclib in ER+ breast cancer models, and in addition sensitised triple negative breast cancer models to palbociclib. Moreover, GPX4 null xenografts were highly sensitive to palbociclib in vivo. Transcriptomics and proteomics analysis showed that palbociclib upregulate pathways involved in oxidative stress and lipid metabolism promoting a redox-lipid imbalance. Palbociclib induced lipid peroxidation leading to a ferroptosis vulnerable state with GPX4 preventing cell death. Polyunsaturated fatty acids (PUFAs) are highly susceptible of lipid peroxidation, and pathways that regulate their abundance in membrane phospholipids were explored. Interestedly, in ER+ breast cancer models, lipid peroxidation relied on a peroxisome AGPAT3-dependent pathway rather than the classical ACSL4 pathway.

Conclusion:

Our studies demonstrate that quiescence induced by palbociclib results in a ferroptosis-vulnerable state that could be exploited through combination with GPX4 inhibitors to enhance sensitivity to CDK4/6 inhibition in breast cancer.

Citation Format: Maria Teresa Herrera Abreu, Uzma Khalid, Jian Ning, Rosalind Cutts, Gemma Wilson, Christopher Lord, Amanda Swain, Nicholas Turner. Inhibition of GPX4 enhances CDK4/6 inhibitor activity in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS12-04.
Abstract SoA1-02: Engineered T cell therapies- what is the outlook for breast cancer?
Authors: Velez V. Hoyos
Published: May 2024

With the promising outcomes seen in hematological malignancies, engineered T-cell therapies, notably chimeric antigen receptor (CAR) therapies, have emerged as breakthroughs in the field of oncology. Yet, their prospect in treating breast cancer and other solid tumors remains a topic of intense investigation. This presentation aims to delve into the diverse engineered T-cell treatments, contextualizing their role in breast cancer. We explore the intrinsic therapeutic challenges these modalities face and the concerted efforts in the scientific community to overcome them. We will look at the current clinical trial landscape for CAR-T cell therapies in breast cancer, underscoring their potential in shaping breast cancer treatment in the years to come.

Citation Format: V. Hoyos Velez. Engineered T cell therapies- what is the outlook for breast cancer? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA1-02.
Abstract SoA2-01: Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity
Authors: Ruscetti M.
Published: May 2024

Cellular senescence is a stress-induced program following aberrant oncogene activation or administration of cancer therapies, including chemotherapeutic agents and CDK4/6 inhibitors commonly used for treating advanced breast cancers, that results in the proliferative arrest of damaged cells and induction of the senescence associated secretory phenotype (SASP). The SASP involves secretion of inflammatory cytokines and chemokines and upregulation of immunomodulatory cell surface molecules on senescent cells that can promote their clearance by the immune system and tumor resolution. However, if left unchecked, the chronic SASP can also lead to immune suppression and further tissue damage that drives tumor dissemination and metastasis. Here we will discuss our efforts to understand how the SASP can promote anti-tumor immunity and immunotherapy activity in some cancer contexts yet in others immune suppression and tumor promotion. Our findings in other solid tumor contexts demonstrate that the tissue microenvironment has a profound impact of the type of SASP program activated and SASP-mediated immune responses produced and suggest further therapeutic interventions to remodel the SASP for immune control of cancer. Moreover, our results in other hormone-driven cancers suggest that CDK inhibitor and chemotherapy regimens produce different SASPs and resulting effects on myeloid cell and lymphocyte phenotypes that could explain their varying effects on anti-tumor immunity and treatment outcomes. Collectively these findings have important implications for breast cancer treatment and pave the path for rationale combination therapies with senescence-inducing agents to achieve immune control in breast and other immunologically “cold” solid tumor malignancies that are generally unresponsive to current immunotherapy regimens.

Citation Format: M. Ruscetti. Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA2-01.
Abstract SS02-03: Cancer risk associated with exogenous hormone use in BRCA mutation carriers
Authors: Kotsopoulos J.
Published: May 2024

Women with a pathogenic vari ant (mutation hereafter) in the BRCA1 or BRCA2 gene face the highest known lifetime risks of developing breast cancer. Notably, incidence rates increase rapidly in early adulthood but remain high even after age 60. Thus, understanding how exogenous (anti)hormones impact these risks is important for the safe clinical management of high-risk women, especially following early surgical menopause. In this session, I will review the current data on the role of tamoxifen chemoprevention, as well as the impact of oral contraceptives, hormone replacement therapy and fertility medication on breast cancer risk. Where possible, I will also discuss associations with ovarian cancer, given that managing BRCA-cancer risks is a balancing act, and present findings by gene mutation. Gaps in the literature and opportunities for further research will also be described. Our goal should be to maximize survival while optimizing health following risk-reducing salpingo-oophorectomy.

Citation Format: J. Kotsopoulos. Cancer risk associated with exogenous hormone use in BRCA mutation carriers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SS02-03.
Abstract Wrk2-01: Organoid Models of Cancer and the Tumor Microenvironment
Authors: Kuo C.
Published: May 2024

Both cell-intrinsic and microenvironmental influences vitally govern tumor progression. Mutational, chromosomal and epigenetic alterations represent the former, while the latter is influenced by diverse stromal populations including fibroblasts, vasculature and immune cells. In vitro organoid culture provides an experimentally tractable platform for cancer research that is applicable to cell-autonomous and tumor microenvironmental studies. The first part of this lecture will describe our work using organoid culture to functionally validate tumor cell-intrinsic genomic alterations. Notably, cancer research has traditionally lacked in vitro methods where tumors can be holistically cultured in a non-reconstitutive manner that co-preserves neoplastic cells together with endogenous stromal components. Thus, the second part of this lecture will describe advances in 3D tumor organoid culture that allow growth of cancer cells in a manner that preserves their native interaction with diverse tumor-infiltrating immune cells and allows analysis of immune checkpoint inhibition.

Citation Format: C. Kuo. Organoid Models of Cancer and the Tumor Microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-01.
Abstract Wrk2-02: Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability
Authors: Laughney A.
Published: May 2024

Multicellular programs underly emergent phenotypes in health and disease. Yet, deciphering the functional effects of interactions amongst cell types remains a major challenge. Cells typically send messages to their microenvironment by emitting ligands, which bind to complimentary receptors on the surfaced of target cells; then triggering a change in the behavior of the target cell. Complimentary ligand-receptor-pairs are well annotated and methods have been developed to infer cell-cell interactions from single cell expression data based on their mutual expression. However, these methods do not assess the effect of ligand-receptor-mediated interactions on the microenvironment. Thus, we developed ContactTracing – a fundamentally new, systems level approach that exploits inter- and intra-sample variability to infer ligand effects on gene expression in target (receptor-expressing) cells without prior knowledge of downstream signaling (Nature, 2023). Foundational work towards benchmarking and validation of this method was performed in isogenic breast cancer models distinguished by tumor cell-intrinsic rates of chromosome missegregation (a cellular process called chromosomal instability, or CIN). Through this, we identified tumor ligands emanating from an endoplasmic reticulum (ER)-stress response as potential mediators of immune suppression in chromosomally unstable tumors. Indeed, CIN-induced chronic STING activation led to rapid interferon-selective desensitization and a switch to ER-stress-dependent transcription. Moreover, inhibition of chronic STING - or key mediators of its unfolded protein response to ER-stress - suppressed metastasis in syngeneic models of melanoma, breast and colorectal cancer; validating this innovative methodology and identifying a targetable mediator of cancer metastasis.

Citation Format: A. Laughney. Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-02.
Supplementary Figure 2 from ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D.
Published: May 2024

ROR2 promotes mesothelial clearance in OVCAR3 and OVCAR8 tumor cells
Supplemental Table 3 from ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D.
Published: May 2024

Supplemental Table 3. screen results
Supplementary Figure 1 from SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter
Authors: Zhu Minhui , Ma Yi , Wang Wei , Li Meng , Chen Shicai , Liu Fei , Shi Xiaoqiong , Bi Hongsen , Zhang Chen , Nie Fangfei , Zheng Hongliang , Zhang Caiyun
Published: May 2024

Supplementary Figure 1. Validation of three SCUBE3 shRNA clones was performed by qPCR analysis. Results were presented as mean ± SD. **P<0.01.
Supplementary Table 8 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 8. LuCaP Phosphoproteome VSN Normalized
Supplementary Table 15 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 15. LuCaP NE Functional Phosphoproteome
Supplementary Table 14 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Table 14. LuCaP AdCa Functional Phosphoproteome
Supplementary Figure 1 from Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: May 2024

Supplementary Figure 1. Sample processing workfow after raw fles were searched using MaxQuant spectra matching to a peptide sequence, for the proteome (green) and for the phosphoproteome (magenta).
Supplementary Figure 5 from An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression
Authors: Prasad Hari , Mandal Susmita , Mathew John Kandam Kulathu , Cherukunnath Aparna , Duddu Atchuta Srinivas , Banerjee Mallar , Ramani Harini , Bhat Ramray , Jolly Mohit Kumar , Visweswariah Sandhya S.
Published: May 2024

Supplementary Figure 5 shows NHE9 expression in primary and metastatic colorectal cancer patient samples.
Data from ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D.
Published: May 2024

Abstract
Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate noncanonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular high-throughput genetic screen, we independently identified ROR2 as a driver of ovarian tumor cell adhesion and invasion. ROR2 expression in ovarian tumor cells serves to drive directed cell migration preferentially toward areas of high Wnt5a ligand, such as the mesothelial lined omentum. In addition, ROR2 promotes ovarian tumor cell adhesion and clearance of a mesothelial monolayer. Depletion of ROR2, in tumor cells, reduces metastatic tumor burden in a syngeneic model of ovarian cancer. These findings support the role of ROR2 in ovarian tumor cells as a critical factor contributing to the early steps of metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer.
Implications:
This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
Supplementary Figure S1 from Examining the Association between Abstinence from Smoking and Healthcare Costs among Patients with Cancer
Authors: Kypriotakis George , Kim Seokhun , Karam-Hage Maher , Robinson Jason D. , Minnix Jennifer A. , Blalock Janice A. , Cui Yong , Beneventi Diane , Kim Bumyang , Pan I.-Wen , Shih Ya-Chen Tina , Cinciripini Paul M.
Published: May 2024

Supplementary Figure S1: Covariate balance before and after applying inverse probability of treatment weights (IPTW).
Supplementary Table S1 from Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Shen Yajing , Chen Jiajun , Wu Jinyu , Li Tiandong , Yi Chuncheng , Wang Keyan , Wang Peng , Sun Changqing , Ye Hua
Published: May 2024

Supplementary Table S1: We applied 52 serum samples to the HuProt™ microarray and detected autoantibody signals in 10 pooled HCC samples and 10 pooled normal control (NC) samples, including 30 HCC patients and 22 NCs. Samples were merged based on age and gender to ensure consistency. For the HCC group, ten pooled samples were created by mixing every three sera. As for the NC group, six pooled samples were generated by mixing every three sera, while the remaining four samples were used separately (Supplementary Table S1).
Supplementary Figure S5 from Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Shen Yajing , Chen Jiajun , Wu Jinyu , Li Tiandong , Yi Chuncheng , Wang Keyan , Wang Peng , Sun Changqing , Ye Hua
Published: May 2024

Supplementary Figure S5: In the training set, the AUC for identifying HBV-HCC patients from CHB patients 0.788 (95% CI: 0.733-0.843) (Supplementary Figure S5A). Similarly, the AUC of the panel was 0.764 (95% CI: 0.695-0.833) in the test-set (Supplementary Figure S5B). In the training set, the AUC for identifying HBV-HCC patients from HBV-LC patients was 0.646 (95% CI: 0.576-0.716) (Supplementary Figure S5C). In the test set, the AUC for identifying HBV-HCC patients from HBV-LC patients was 0.595 (95% CI: 0.507-0.684) (Supplementary Figure S5D).
Supplementary Table 3 from Triple Primary Cancers: An Analysis of Genetic and Environmental Factors
Authors: Borja Nicholas A. , Silva-Smith Rachel , Calfa Carmen , Sussman Daniel A. , Tekin Mustafa
Published: May 2024

Supplementary Table 3: Summary of patients without hereditary cancer susceptibility identified in the MPC cohort
Data from Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Shen Yajing , Chen Jiajun , Wu Jinyu , Li Tiandong , Yi Chuncheng , Wang Keyan , Wang Peng , Sun Changqing , Ye Hua
Published: May 2024

Abstract
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772–0.897] for this panel and 0.727 (95% CI, 0.642–0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734–0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection.
Prevention Relevance:
We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.
Data from Triple Primary Cancers: An Analysis of Genetic and Environmental Factors
Authors: Borja Nicholas A. , Silva-Smith Rachel , Calfa Carmen , Sussman Daniel A. , Tekin Mustafa
Published: May 2024

Abstract
The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk.
Prevention Relevance:
In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility.

See related Spotlight, p. 193
Table S1, Table S2, Table S3, Table S4 from Co-clinical Trial of Novel Bispecific Anti-HER2 Antibody Zanidatamab in Patient-Derived Xenografts
Authors: DiPeri Timothy P. , Evans Kurt W. , Wang Bailiang , Zhao Ming , Akcakanat Argun , Raso Maria Gabriela , Rizvi Yasmeen Q. , Zheng Xiaofeng , Korkut Anil , Varadarajan Kaushik , Uzunparmak Burak , Dumbrava Ecaterina E. , Pant Shubham , Ajani Jaffer A. , Pohlmann Paula R. , Jensen V. Behrana , Javle Milind , Rodon Jordi , Meric-Bernstam Funda
Published: May 2024

Supplementary Table 1: Genomic and biomarker data of zanidatamab co-clinical trial xenograft models.

Genomic and biomarker data of zanidatamab co-clinical trial xenograft models. Patient biomarkers/NGS has four categories: (+), (-), N/A, and Gain

Supplementary Table 2: Event-free survival and relative treatment-to-control ratios for co-clinical trial PDXs.

Event-free survival and relative treatment-to-control ratios for co-clinical trial PDXs.

Supplementary Table 3. Event-free survival of PDXs compared to patient response.

Event-free survival of PDXs compared to patient response.

Supplementary Table 4. Immunohistochemistry antibodies.
Figure S4 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Authors: Yang Jiuling , Wang Li , Byrnes James R. , Kirkemo Lisa L. , Driks Hannah , Belair Cassandra D. , Aguilar Oscar A. , Lanier Lewis L. , Wells James A. , Fong Lawrence , Blelloch Robert
Published: May 2024

Supplementary Figure S4: PVRL2 functions independently of PVRIG and TIGIT pathways.
Figure S3 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Authors: Yang Jiuling , Wang Li , Byrnes James R. , Kirkemo Lisa L. , Driks Hannah , Belair Cassandra D. , Aguilar Oscar A. , Lanier Lewis L. , Wells James A. , Fong Lawrence , Blelloch Robert
Published: May 2024

Supplementary Figure S3: PVRL2 regulates CD8 T cell and NK cell activation.
Figure S3 from High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance
Authors: Saeed Muhammad A. , Peng Bo , Kim Kevin , Rawat Kavita , Kuehm Lindsey M. , Siegel Zoe R. , Borkowski Ariel , Habib Nabih , Van Tine Brian , Sheikh Nadeem , Tuyen Vu , Thorek Daniel L.J. , Fehniger Todd A. , Pachynski Russell K.
Published: May 2024

IL-15 dose response in sipuleucel-T
Supplementary Table S5 from Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer
Authors: Blise Katie E. , Sivagnanam Shamilene , Betts Courtney B. , Betre Konjit , Kirchberger Nell , Tate Benjamin J. , Furth Emma E. , Dias Costa Andressa , Nowak Jonathan A. , Wolpin Brian M. , Vonderheide Robert H. , Goecks Jeremy , Coussens Lisa M. , Byrne Katelyn T.
Published: May 2024

Supplementary Table S5. Quantification of T cell Functionality Barcodes.
Figure S2 from ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms
Authors: Tian Jane , Ashique Amir M. , Weeks Sabrina , Lan Tian , Yang Hong , Chen Hung-I Harry , Song Christina , Koyano Kikuye , Mondal Kalyani , Tsai Daniel , Cheung Isla , Moshrefi Mehrdad , Kekatpure Avantika , Fan Bin , Li Betty , Qurashi Samir , Rocha Lauren , Aguayo Jonathan , Rodgers Col , Meza Marchelle , Heeke Darren , Medfisch Sara M. , Chu Chun , Starck Shelley , Basak Nandini Pal , Sankaran Satish , Malhotra Mohit , Crawley Suzanne , Tran Thomas-Toan , Duey Dana Y. , Ho Carmence , Mikaelian Igor , Liu Wenhui , Rivera Lee B. , Huang Jiawei , Paavola Kevin J. , O'Hollaren Kyle , Blum Lisa K. , Lin Vicky Y. , Chen Peirong , Iyer Anjushree , He Sisi , Roda Julie M. , Wang Yan , Sissons James , Kutach Alan K. , Kaplan Daniel D. , Stone Geoffrey W.
Published: May 2024

Supplementary Figure S2
Figure S11 from ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms
Authors: Tian Jane , Ashique Amir M. , Weeks Sabrina , Lan Tian , Yang Hong , Chen Hung-I Harry , Song Christina , Koyano Kikuye , Mondal Kalyani , Tsai Daniel , Cheung Isla , Moshrefi Mehrdad , Kekatpure Avantika , Fan Bin , Li Betty , Qurashi Samir , Rocha Lauren , Aguayo Jonathan , Rodgers Col , Meza Marchelle , Heeke Darren , Medfisch Sara M. , Chu Chun , Starck Shelley , Basak Nandini Pal , Sankaran Satish , Malhotra Mohit , Crawley Suzanne , Tran Thomas-Toan , Duey Dana Y. , Ho Carmence , Mikaelian Igor , Liu Wenhui , Rivera Lee B. , Huang Jiawei , Paavola Kevin J. , O'Hollaren Kyle , Blum Lisa K. , Lin Vicky Y. , Chen Peirong , Iyer Anjushree , He Sisi , Roda Julie M. , Wang Yan , Sissons James , Kutach Alan K. , Kaplan Daniel D. , Stone Geoffrey W.
Published: May 2024

Supplementary Figure S11
Figure S3 from Chronic Stress Exacerbates the Immunosuppressive Microenvironment and Progression of Gliomas by Reducing Secretion of CCL3
Authors: Wang Xu , Zhang Long , Zhou Yi , Wang Yan , Wang Xiang , Zhang Yining , Quan Ankang , Mao Yufei , Zhang Yu , Qi Ji , Ren Zhongyu , Gu Linbo , Yu Rutong , Zhou Xiuping
Published: May 2024

Supplementary Figure 3. Blocking the stress reverses the levels of IFN-γ and GZMB in gliomas (Related to Fig.3)
Figure S4 from ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma
Authors: Xu Licheng , Li Wenjing , Liu Danxi , Cao Jing , Ge Jingchun , Liu Xinyu , Wang Yue , Teng Yujian , Liu Pengyan , Guo Xinyue , He Chen , Liu Ming , Tian Linli
Published: May 2024

Figure S4. ANXA3 has no effect on ferroptosis in macrophages.
Data from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Authors: Yang Jiuling , Wang Li , Byrnes James R. , Kirkemo Lisa L. , Driks Hannah , Belair Cassandra D. , Aguilar Oscar A. , Lanier Lewis L. , Wells James A. , Fong Lawrence , Blelloch Robert
Published: May 2024

Abstract
Poliovirus receptor-related 2 (PVRL2, also known as nectin-2 or CD112) is believed to act as an immune checkpoint protein in cancer; however, most insight into its role is inferred from studies on its known receptor, poliovirus receptor (PVR)-related immunoglobulin domain protein (PVRIG, also known as CD112R). Here, we study PVRL2 itself. PVRL2 levels were found to be high in tumor cells and tumor-derived exosomes. Deletion of PVRL2 in multiple syngeneic mouse models of cancer showed a dramatic reduction in tumor growth that was immune dependent. This effect was even greater than that seen with deletion of PD-L1. PVRL2 was shown to function by suppressing CD8+ T and natural killer cells in the tumor microenvironment. The loss of PVRL2 suppressed tumor growth even in the absence of PVRIG. In contrast, PVRIG loss showed no additive effect in the absence of PVRL2. T-cell immunoreceptor with Ig and ITIM domains (TIGIT) blockade combined with PVRL2 deletion resulted in a near complete block in tumor growth. This effect was not recapitulated by the combined deletion of PVRL2 with its paralog, PVR, which is the ligand for TIGIT. These data uncover PVRL2 as a distinct inhibitor of the antitumor immune response with functions beyond that of its known receptor PVRIG. Moreover, the data provide a strong rationale for combinatorial targeting of PVRL2 and TIGIT for cancer immunotherapy.
Table S2 from De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Authors: Tangudu Naveen Kumar , Buj Raquel , Wang Hui , Wang Jiefei , Cole Aidan R. , Uboveja Apoorva , Fang Richard , Amalric Amandine , Yang Baixue , Chatoff Adam , Crispim Claudia V. , Sajjakulnukit Peter , Lyons Maureen A. , Cooper Kristine , Hempel Nadine , Lyssiotis Costas A. , Chandran Uma R. , Snyder Nathaniel W. , Aird Katherine M.
Published: May 2024

Primers used in this study
Table S1 from De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Authors: Tangudu Naveen Kumar , Buj Raquel , Wang Hui , Wang Jiefei , Cole Aidan R. , Uboveja Apoorva , Fang Richard , Amalric Amandine , Yang Baixue , Chatoff Adam , Crispim Claudia V. , Sajjakulnukit Peter , Lyons Maureen A. , Cooper Kristine , Hempel Nadine , Lyssiotis Costas A. , Chandran Uma R. , Snyder Nathaniel W. , Aird Katherine M.
Published: May 2024

CRISPR KO library containing 128 genes comprising the nucleotide metabolism signature
Figure S4 from De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Authors: Tangudu Naveen Kumar , Buj Raquel , Wang Hui , Wang Jiefei , Cole Aidan R. , Uboveja Apoorva , Fang Richard , Amalric Amandine , Yang Baixue , Chatoff Adam , Crispim Claudia V. , Sajjakulnukit Peter , Lyons Maureen A. , Cooper Kristine , Hempel Nadine , Lyssiotis Costas A. , Chandran Uma R. , Snyder Nathaniel W. , Aird Katherine M.
Published: May 2024

shp16 tumor bearing mice treated with methotrexate have a trend towards a survival advantage; and methotrexate does not affect body weight or blood cell counts. Related to Figure 5.
Figure S3 from De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Authors: Tangudu Naveen Kumar , Buj Raquel , Wang Hui , Wang Jiefei , Cole Aidan R. , Uboveja Apoorva , Fang Richard , Amalric Amandine , Yang Baixue , Chatoff Adam , Crispim Claudia V. , Sajjakulnukit Peter , Lyons Maureen A. , Cooper Kristine , Hempel Nadine , Lyssiotis Costas A. , Chandran Uma R. , Snyder Nathaniel W. , Aird Katherine M.
Published: May 2024

Anti-folates induce death and increased DNA damage foci in shCdkn2a cells; shp16 cells do not mount a robust senescence-associated secretory phenotype (SASP) in response to Palbociclib; anti-proliferative effects of anti-folates are longer-lived than palbociclib; and folate transporters are upregulated in shp16/shCdk2na cells. Related to Figure 4.