bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5923: The genetic landscape of metastatic breast cancer reflected in circulating tumor DNA
Authors: Kavan Stephanie
Published: April 2023

Tissue biopsies of breast tumors only provide a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. Plasma-derived cell-free tumor DNA constitutes a potential surrogate for tumor DNA obtained from tissue biopsies to potentially capture inter-and intra-tumoral heterogeneity present in metastatic breast cancer. We aimed to investigate to what extent variants identified in the primary tumor and metastases are reflected in plasma. We performed whole-exome sequencing on tumor DNA from primary and metastatic lesions and plasma-derived circulating tumor DNA of eight patients with metastatic breast cancer. Our results show that metastases most often follow parallel evolution, given the low levels of stem mutations detected between primary tumors and matched metastases and mutational events private to the primary tumor. Furthermore, we demonstrated that ctDNA mainly reflected old stem mutations shared between primary tumor and metastasis, and less often, genetic alterations found solely in primary tumor or metastasis. Lastly, clinically relevant variants, e.g., resistance mutations detected in primary tumor and metastasis, were to some extent reflected in ctDNA, including affected genes MET, MTOR, CDK6, PIK3CA, and GATA3. However, mutations in MED1, NCOR1, and NCOR2 were only found in tumor tissues. These findings support the importance of a metastatic deposit biopsy to guide treatment decisions. Together, our results have implications for future ctDNA studies. For monitoring tumor burden using ctDNA, our results suggest that truncal mutations are the best candidates, as they are highest in circulating levels. For confident tracking of subclonal mutations in ctDNA, liquid biopsies are not yet to substitute metastatic tissue biopsies and instead demonstrate support to the current gold standard.

Citation Format: Stephanie Kavan. The genetic landscape of metastatic breast cancer reflected in circulating tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5923.
Abstract 5950: Ccr2+ monocyte derived macrophages influence trajectories of acquired therapy resistance in BRAF-mutant melanoma
Authors: Kim Dahihm , An Luye , Moon Jiwon , White Andrew
Published: April 2023

Therapies targeting oncogene addiction have had a tremendous impact on patient care, but drug resistance continues to be problematic. One method to deal with this challenge entails extending the scope of anti-cancer treatment beyond tumor cells by additionally altering their tumor microenvironment. Understanding how the tumor microenvironment can contribute to the evolution of diverse resistance pathways could aid in the rational design of sequential treatments that enforce pressure towards a more predictable resistance trajectory. Tumor associated macrophages often support neoplastic growth and are frequently the most abundant immune cell found in tumors. Here, we used clinically relevant in vivo Braf-mutant melanoma models and Ccr2-RFP; Cx3cr1-GFP mice to track the long-term changes in tumor cells and macrophages under targeted therapy with Braf/Mek inhibitors. We assessed the dynamic evolution of the macrophage population generated by therapy pressure-induced stress. During the onset of a drug-tolerant persister state, Ccr2+ macrophage infiltration rises, underscoring a prominent role at this point in melanoma evolution for development of drug-resistance. Importantly, we show that a lack of melanoma infiltrating Ccr2+ macrophages delays onset of resistance. In this case, rebounded tumor cells from Ccr2 knockout recipients favor the evolution of cell-extrinsic mediated resistance mechanisms, which can be reversed when these adapted melanoma cells are relocated to a microenvironment with functional Ccr2. Conversely, Ccr2 presence promotes development of cell-intrinsic drug resistance with a stable phenotype in rebounded tumor cells. Overall, this demonstrates that the development of resistance may be manipulated and directed to improve timing and probability of relapse.

Citation Format: Dahihm Kim, Luye An, Jiwon Moon, Andrew White. Ccr2+ monocyte derived macrophages influence trajectories of acquired therapy resistance in BRAF-mutant melanoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5950.
Abstract 5954: Germline epitopes modulate immune surveillance informing breast cancer subtypes
Authors: Houlahan Kathleen , Khan Aziz , Curtis Christina
Published: April 2023

Cancer represents a wide spectrum of molecularly and morphologically diverse diseases. Individuals with the same histopathological classification can have tumors with drastically different molecular profiles and clinical responses to treatment. It remains unclear as to when during the disease course these differences arise and why some tumors are addicted to one oncogenic pathway over another. Somatic genomic aberrations occur within the context of an individual’s germline genome, which can vary across millions of germline polymorphisms. It is unknown the extent to which germline differences influence the somatic evolution of a tumor. Interrogating 4,912 breast cancer lesions, spanning pre-invasive to metastatic disease, we demonstrate that germline variants in highly expressed and amplified genes influence somatic evolution by modulating immunoediting at early stages of tumor development. Specifically, we show that the burden of germline-derived epitopes in recurrently amplified genes selects against somatic gene amplification in pre-invasive and invasive breast cancer. As a representative example, individuals with high burden of germline-derived epitopes in ERBB2 are significantly less likely to develop HER2+ breast cancer than ER+ or triple negative breast cancer. The same negative association between epitope burden and somatic amplification is observed for four recurrent amplicons observed in high risk ER+ breast tumors. No association was observed between somatic amplifications and epitope burden in metastatic breast cancer suggesting a subset of tumors are able to overcome immune-mediated negative selection. Tumors that do are more aggressive and demonstrate an “immune cold” phenotype. Taken together, these data show the germline genome plays a pivotal role in dictating somatic evolution in breast cancer. Exploiting germline-mediated immunoediting may facilitate the development of blood-based biomarkers that refine risk stratification within breast cancer subtypes.

Citation Format: Kathleen Houlahan, Aziz Khan, Christina Curtis. Germline epitopes modulate immune surveillance informing breast cancer subtypes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5954.
Abstract 6755: The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients
Authors: Tseng Kuan-Yu , Chou Cheng-Wei
Published: April 2023

Introduction Pancreatic adenocarcinoma (PDAC) is a highly aggressive malignancy with significant morbidity and mortality. RAS (renin-angiotensin system) inhibitors have been used for hypertension, and the potential role of using RAS inhibitors in pancreatic adenocarcinoma have been investigated in pre-clinical models by enhancing drug delivery and reducing hypoxia. However, the clinical benefit of RAS inhibitors in pancreatic cancer patients was still unclear.

Methods We retrospectively investigated the impact of RAS inhibitors on survival outcomes of pancreatic adenocarcinoma patients in Taichung Veterans General Hospital between January 2014 and July 2021. Patients with histologically proven pancreatic adenocarcinoma were included in the study. Clinical feature with drugs exposure and survival outcome were analyzed.

Results A total of 384 pancreatic cancer patients were analyzed. Among them, 70 patients had concurrent use of RAS inhibitors and 314 patients had no concurrent medication use. Among patients with RAS inhibitors use, the diagnosed age was significantly older (70.0 vs. 68.0, p = 0.023), and a higher proportion of hypertension (100.0% vs. 51.0%, p < 0.0001), chronic kidney disease (27.5% vs. 9.1%, p < 0.0001), and diabetes (64.3% vs 39.5%, p < 0.0001) than those without RAS inhibitors use. The 12-month progression-free survival were 22.9% and 13.7% in the RAS inhibitors and control group (p = 0.008), respectively. The Overall survival was not significantly different in the both groups (p = 0.356). In the multivariate analysis, the use of RAS inhibitors had a significantly better progression-free survival outcome (Hazard ratio = 0.025, CI:0.52-0.96). The advanced disease status, poor ECOG performance status and the elevated level of CA19-9 were correlated with poor progression-free survival.

Conclusion In our study, although higher percentage of existed comorbidities in the RAS inhibitor group, we demonstrated that the use of RAS inhibitors among pancreatic cancer patients might provide a better progression-free survival outcome. Further prospective study and investigation are warranted.

Citation Format: Kuan-Yu Tseng, Cheng-Wei Chou. The impact of renin-angiotensin system inhibitors on survival outcomes of pancreatic adenocarcinoma patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6755.
Abstract 676: Neuro-oncology imaging mass cytometry panels enable spatial investigation of brain tumor microenvironment
Authors: Zabinyakov Nick , Raza Qanber , Loh Christina
Published: April 2023

Brain neoplasms represent a complex form of cancer that is one of the most challenging to classify and treat. Over 120 different tumor subtypes originate from various parts of the central nervous system, which makes identifying the composition of the tumor microenvironment (TME) vital for early assessment of progression, treatment, and prevention. We developed high-plex proteomic analysis tools to thoroughly characterize the TME of both human and mouse brain tissues using Imaging Mass Cytometry™ (IMC™). IMC offers unprecedented insight into the TME by uncovering the spatial distribution of 40-plus distinct molecular markers without autofluorescence, facilitating the research of brain neoplasms. Here, we demonstrate the application of high-plex human and mouse neuro-oncology IMC panels on normal and tumor formalin-fixed paraffin-embedded brain tissues.

A basic neurophenotyping panel was developed and used to customize the Maxpar® Human and Maxpar OnDemand™ Mouse Immuno-Oncology IMC Panel Kits. Human and mouse neuro-oncology panels provide deep phenotyping and characterization of brain TME composition. These neuro panels consist of cross-reactive clones and enable flexible panel design for brain-specific research goals, such as brain tumor classification, and assessment of neuronal inflammation, degeneration, and development.

We applied the neuro-oncology panels on tissue microarrays (TMAs) containing a variety of human brain tumors and mouse glioblastoma and neuroblastoma tissues. Normal brain tissues were used for comparative analysis as controls. The Hyperion™ Imaging System was utilized to digitize images from the tissues followed by quantitative analysis to assess the cellular composition of normal and cancerous brain TME.

We successfully identified major cell populations that make up human and mouse brain matter, such as neurons, astrocytes, microglia, and oligodendrocytes. Various tumor cell phenotypes, resident and infiltrating cells, and resting and activated microglia were detected in multiple tumor subtypes. Subsequent single-cell analysis provided a comprehensive and quantitative assessment of the brain TME in our samples. We classified the distinct states of neurons and quantified myeloid and lymphoid immune cell infiltration across normal, astrocytoma, and glioblastoma tissues.

Empowered by high-plex neuro-oncology panels, IMC can accelerate brain tumor research and provide insights into the spatial complexity of neuronal neoplasms.

Citation Format: Nick Zabinyakov, Qanber Raza, Christina Loh. Neuro-oncology imaging mass cytometry panels enable spatial investigation of brain tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 676.
Abstract 68: Dissecting cellular and molecular alterations in pre-invasive to invasive lung cancer progression at single-cell resolution
Authors: Yoffe Liron , Borczuk Alain , McGraw Timothy E. , Elemento Olivier , Altorki Nasser K. , Mittal Vivek
Published: April 2023

Non-small cell lung cancer (NSCLC) accounts for most cancer-related deaths worldwide, largely due to diagnosis at advanced metastatic stages. Increased implementation of low-dose computed tomography (CT)-guided screening has led to the identification of non-solid lesions or ground-glass opacities (GGOs) that are not visible on plain chest radiography and can harbor very early-stage tumors. Growth of the lesions and/or development of a solid component can indicate more aggressive behavior. Using the low-dose CT reduced lung cancer mortality by >20%, underscoring the need for early detection and intervention. However, the cellular and molecular determinants that contribute to the malignant progression of those early preinvasive lesions remain poorly understood. To assess intratumoral heterogeneity and associated dynamic changes in the immune contexture during early lung carcinogenesis, we performed single-cell RNA-seq and Hyperion imaging on surgically resected freshly harvested tissues from 21 patients (matched solid and non-solid components of lesions and adjacent non-involved lungs), representing a spectrum from preneoplasia to invasive disease. Analysis of >300K cells identified cellular, transcriptomic, and metabolic alterations as well as tumor-stroma cross-talk pathways. Specifically, preinvasive to invasive disease progression was associated with significant changes in the immune landscape determined by an increase in exhausted CD4/CD8 T-cells, suppressive T-regs, polymorphonuclear myeloid-derived suppressor cells, and M2-like macrophages; and a decrease in cytotoxic CD8 T-cells, NK cells, and inflammatory cDC2 cells, suggesting that activation of immunosuppressive/anti-inflammatory microenvironment and suppression of immune activation microenvironment may enable tumor progression.

Citation Format: Liron Yoffe, Alain Borczuk, Timothy E. McGraw, Olivier Elemento, Nasser K. Altorki, Vivek Mittal. Dissecting cellular and molecular alterations in pre-invasive to invasive lung cancer progression at single-cell resolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 68.
Abstract 693: A novel multi-subset dendritic cell vaccine derived from hematopoietic progenitor cells
Authors: Yu Chun , Barrett Richard L. , Zutshi Ananya , Palucka Karolina
Published: April 2023

Owing to their molecular features, tissue localization and antigen processing and presentation capacity, dendritic cells (DCs) induce and regulate T cell immunity including licensing T cells to kill target cells. However, tumors often suppress DC differentiation and function leaving cancer patients with DC populations that are quantitatively and qualitatively deficient. This limits both the native immune responses to tumors as well as response to cancer therapy including immunotherapy. Thus, provision of healthy and functionally intact DCs to replace and correct the in vivo function offers an interesting therapeutic opportunity. DCs are composed of multiple subsets which specialize in activation of different immune effectors. Thus, a combination of DC subsets could generate a broad and diverse immunity targeted at cancer. To date, several attempts have been made to generate functional human DCs ex vivo for injection to patients, but the DC subtypes most effective in generation of anti-tumor responses—cDC1 and cDC2s—have proven difficult to make ex vivo using clinically compliant protocols. Here we show that cDC1s and cDC2s can be generated at high yield from hematopoietic progenitor cells (HPCs) from three different HPCs sources (including adult bone marrow) using clinically compliant protocols. We characterize the phenotype and functionality of these cells showing that both cDC1s and cDC2s efficiently process antigens, stimulate, and expand T cells specific for those antigens, and that those T cell populations display targeted killing of tumor cells in vitro. The ability to produce these subtypes using clinically compliant protocols is a major step towards developing effective autologous DC therapy for cancer patients.

Citation Format: Chun Yu, Richard L. Barrett, Ananya Zutshi, Karolina Palucka. A novel multi-subset dendritic cell vaccine derived from hematopoietic progenitor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 693.
Abstract 698: Developing a self-targeted cancer immunotherapy using engineered whole tumor cell-based vaccine
Authors: Chen Kok-Siong , Mendonca Natalia Claire , Borges Paulo , Shah Khalid
Published: April 2023

The administration of inactivated tumor cell lysate is known to induce a potent antitumor immune response, however, their therapeutic efficacy as shown in Phase I-III clinical trials is limited. This could be attributed to the lack of direct cytotoxic effect on tumor cells and the inability to trigger a strong antitumor immune response. Unlike inactivated tumor cells, living tumor cells possess a unique potential to home to and self-target tumors. Therefore, repurposing the tumor cells’ self-homing property and natural source of neoantigens is advantageous for self-targeted cancer immunotherapy. In this study, we developed a genetically engineered living whole cancer cell-based therapeutic with direct tumor killing and immunostimulatory roles. We switched the tumor cells from death ligands sensitive to resistant using CRISPR/Cas9 and subsequently engineered them to release dual cell killing and immunomodulatory agents. These engineered therapeutic tumor cells (ThTC) eliminated established tumor and activating antitumor immune cell trafficking and antigen-specific T cell activation signaling. This mechanism-based efficacy of ThTC translated into a marked survival benefit and long-term immunity in primary, recurrent, and metastatic cancer models in immunocompromised, immunocompetent and humanized mice. Arming naturally neoantigen-rich tumor cells with multidisciplinary therapeutics represents promising cell-based immunotherapy for solid tumors and establishes a roadmap towards clinical translation.

Citation Format: Kok-Siong Chen, Natalia Claire Mendonca, Paulo Borges, Khalid Shah. Developing a self-targeted cancer immunotherapy using engineered whole tumor cell-based vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 698.
Abstract 986: A BioPharma best practices framework to enable successful morphology guided spatial biology studies using NanoString GeoMx® Digital Spatial Profiler
Authors: Abad Leslie , McClain Maxine , Bonnevie Edward , Chen Benjamin , Church Sarah , Demirkan Gokhan , Haynes Premi , Hunter Kelly , Kersarwani Anil , Krull David , Liang Yan , Pal Prithwish , Ramos Corinne , Rodriguez Deniliz , Runyon Jessica , Tessier Julien , Anguiano Esperanza
Published: April 2023

The interest and utility of high-plex spatial profiling of RNA and protein biomarkers has increased over the last few years. The implementation of high-plex analyte spatial platforms, such as GeoMx® Digital Spatial Profiler (DSP), is increasing within discovery and development approaches for biomarkers associated with clinical outcome. The surge in spatial platforms parallels the increase of digital pathology in translational and clinical research studies. The integration of these two workflows has the potential to benefit diagnostic and therapeutic development. This study aims to facilitate the implementation of DSP in tissue analysis workflows helping those involved in drug discovery and development efforts to (1) assess platform feasibility for their research, (2) design effective DSP experiments, and (3) enable generation of high-quality, usable spatial data from large cohort studies. The BioPharma GeoMx DSP Consortium has developed consensus-based best practices incorporating the expertise of panel members via virtual meetings. Best practices guidelines for spatial profiling of tissue biopsies in drug discovery and development using GeoMx stands to advance current standard practices in tissue analysis. These best practices recommendations encompass every step of the implementation of DSP in standard tissue analysis workflows, emphasizing the importance of multidisciplinary stakeholder involvement, testing, defining experimental conditions prior to execution of large-scale studies, and considerations in assessing assay performance. This study offers a practical reference for the optimal implementation of GeoMx DSP in exploratory sample analysis for drug discovery and development studies.

Citation Format: Leslie Abad, Maxine McClain, Edward Bonnevie, Benjamin Chen, Sarah Church, Gokhan Demirkan, Premi Haynes, Kelly Hunter, Anil Kersarwani, David Krull, Yan Liang, Prithwish Pal, Corinne Ramos, Deniliz Rodriguez, Jessica Runyon, Julien Tessier, Esperanza Anguiano. A BioPharma best practices framework to enable successful morphology guided spatial biology studies using NanoString GeoMx® Digital Spatial Profiler [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 986.
Abstract 996: Identification of molecular biomarkers differentiating malignant uterine leiomyosarcoma from benign leiomyoma
Authors: Khamaiseh Sara , Koivisto-Korander Riitta , Ahvenainen Terhi , Bützow Ralf , Mehine Miika , Vahteristo Pia
Published: April 2023

Uterine leiomyosarcomas are rare, aggressive cancers that represent the most common type of uterine sarcomas. They frequently harbor genetic alterations in TP53, RB1, PTEN, and ATRX. Their benign counterpart, uterine leiomyomas (or fibroids) are very common tumors that may significantly affect women’s quality of life. The majority of leiomyomas harbor genetic alterations affecting either MED12, HMGA2, or FH. A third of leiomyosarcomas have been reported to harbor leiomyoma-associated driver mutations, suggesting that some leiomyomas may have undergone malignant transformation. The leiomyoma/leiomyosarcoma diagnosis is largely based on histopathology. This can be specifically challenging in differentiating leiomyosarcomas from a subset of leiomyomas that display histopathological features resembling malignancy. The aim of this study was to identify molecular biomarkers that can accurately differentiate benign and malignant uterine smooth muscle tumors. 3’RNA sequencing of 48 leiomyosarcomas and 44 leiomyomas revealed that leiomyosarcomas are uniquely characterized by dysregulation of the retinoblastoma pathway. We confirmed upregulation of several members of this pathway, including TOP2A and CDK1, in a publicly available transcriptomic dataset of 49 uterine leiomyosarcomas. The second objective of this study was to explore the gene expression profile of leiomyosarcomas carrying leiomyoma-associated driver mutations. This revealed that unlike leiomyomas, leiomyosarcomas do not form distinct gene expression profiles based on the presence of leiomyoma-associated driver mutations such as MED12. However, leiomyosarcomas with a MED12 mutation showed upregulation of RAD51B and ADAM12, which we have previously highlighted as biomarkers of leiomyomas harboring a MED12 mutation. We identified upregulation of IRS4 and characteristic deletions affecting COL4A5 and COL4A6 in four in-house and three additional uterine leiomyosarcomas from The Cancer Genome Atlas (TCGA) collection. Similar driver alterations have previously been reported in a small subset of leiomyomas but not in leiomyosarcomas. In conclusion, leiomyosarcomas display a gene expression profile characterized by dysregulation of genes related to the retinoblastoma pathway. These include potential biomarkers that could be used in a clinical setting to differentiate leiomyosarcomas from leiomyomas.

Citation Format: Sara Khamaiseh, Riitta Koivisto-Korander, Terhi Ahvenainen, Ralf Bützow, Miika Mehine, Pia Vahteristo. Identification of molecular biomarkers differentiating malignant uterine leiomyosarcoma from benign leiomyoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 996.
Abstract SY21-03: Organ-specific responses to targeted and immunotherapies
Authors: Sahai Erik
Published: April 2023

The response to treatment of widely disseminated disease can vary depending on the site of metastasis. In some cases, lesions at one site respond to treatment, while disease at other sites continues to grow. This is seen in the context of melanoma treatment with targeted therapy, with some patients having good responses in the liver, while disease in the brain and bone continues apace. This can be attributed to differences in the microenvironment of lesions in different organs, although other factors undoubtedly contribute. It is also increasingly clear that there is an interplay between the site of metastasis and responses to immunotherapy. Liver metastases are particularly difficult to treat compared to other metastatic locations. Moreover, the presence of liver metastases reduces the efficacy of immunotherapy to control disease at other sites in the same patient. Thus, liver metastases confer systemic tolerance. This is likely linked to the liver being a ‘tolerogenic’ organ with a role in modulating the body’s response to commensal bacteria in the gut. To investigate this, we have established an experimental melanoma model of systemic immune tolerance being conferred by liver metastases. We will present results on the mechanism by which liver metastases hinder not only their response to immunotherapy, but also the response of other distant lesions.

Citation Format: Erik Sahai. Organ-specific responses to targeted and immunotherapies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY21-03.
Abstract SY23-03: Rhabdomyosarcoma: New research tools for precision medicine
Authors: Linardic Corinne Mary
Published: April 2023

Rhabdomyosarcoma (RMS) is a cancer of skeletal muscle histogenesis and the most common soft tissue sarcoma of childhood. Despite decades of basic and clinical research, survival for patients with high-risk disease has not improved since the 1970s, remaining <30% at five years. Genomic landscape studies have identified the most frequently occurring alterations, parsing out fusion-negative RMS driven by RAS pathway mutations, and fusion-positive RMS driven by signature fusion genes including PAX3-FOXO1. However, this information has not yet translated into improved outcomes. Here, we highlight multi-institutional efforts to generate new tools for RMS precision medicine, including the NCI FusOnC2 Cancer Moonshot program to target PAX3-FOXO1, the NCI CCDI Molecular Characterization Initiative to analyze every child’s RMS tumor nucleic acids, and the application of machine learning to RMS tumor images to predict molecular subtype and improve risk stratification.

Citation Format: Corinne Mary Linardic. Rhabdomyosarcoma: New research tools for precision medicine. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY23-03.
Abstract SY30-02: Oncosomes in the early stages of breast cancer
Authors: Kuhn Peter
Published: April 2023

Comprehensive analysis of cellular, acellular and plasma components of the Liquid Biopsy provides the opportunity to investigate cancer evolution and the interactions with the immune system at the systemic level in the individual patient. This presentation will discuss early findings supporting the relevance of oncosomes, large extracellular vesicles, in early-stage breast cancer and its potential utility in early detection and cell-level staging of the disease when combined with the cellular profiles.

Breast cancer (BC) affects 1 in every 8 women in the United States and is currently the most prevalent cancer worldwide. Precise staging at diagnosis and prognosis are essential components for the clinical management of BC patients. We set out to evaluate the feasibility of a next generation liquid biopsy platform to stratify late-stage BC, early-stage BC, and age- and gender matched controls using peripheral blood samples. Utilizing 5 biomarkers, we can identify rare circulating events with epithelial, mesenchymal, endothelial and hematological origin. We detected a higher level of CTCs in late-stage patients, compared to the early-stage and normal donors. We observed more tumor-associated oncosomes in the early-stage, compared to late-stage and the normal donor groups. Overall, we were able to detect reproducible patterns in the enumeration of rare cells and oncosomes of cancer vs. normal donors with an AUC of 99%. An initial concept for cell-level staging with the liquid biopsy was applied to early-stage vs. late-stage BC samples and reached an AUC of 91% allowing for robust stratification.

Citation Format: Peter Kuhn. Oncosomes in the early stages of breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY30-02.
Supplementary Figure S2 from Activation of the FGF2-FGFR1 Autocrine Pathway: A Novel Mechanism of Acquired Resistance to Gefitinib in NSCLC
Authors: Terai Hideki , Soejima Kenzo , Yasuda Hiroyuki , Nakayama Sohei , Hamamoto Junko , Arai Daisuke , Ishioka Kota , Ohgino Keiko , Ikemura Shinnosuke , Sato Takashi , Yoda Satoshi , Satomi Ryosuke , Naoki Katsuhiko , Betsuyaku Tomoko
Published: April 2023

Supplementary Figure S2 - PDF file 411K,Sequencing results of EGFR exon 20 of the genomic DNA extracted from PC9 and HCC827 cells. There was no T790M second mutation of EGFR gene
Supplementary Figure S1 from Activation of the FGF2-FGFR1 Autocrine Pathway: A Novel Mechanism of Acquired Resistance to Gefitinib in NSCLC
Authors: Terai Hideki , Soejima Kenzo , Yasuda Hiroyuki , Nakayama Sohei , Hamamoto Junko , Arai Daisuke , Ishioka Kota , Ohgino Keiko , Ikemura Shinnosuke , Sato Takashi , Yoda Satoshi , Satomi Ryosuke , Naoki Katsuhiko , Betsuyaku Tomoko
Published: April 2023

Supplementary Figure S1 - PDF file 154K, Increased expressions of p-MET and t-MET in HCC827 GR cells
Supplementary Figures 1 - 6 from NF-κB Activation-Induced Anti-apoptosis Renders HER2-Positive Cells Drug Resistant and Accelerates Tumor Growth
Authors: Bailey Shannon T. , Miron Penelope L. , Choi Yoon J. , Kochupurakkal Bose , Maulik Gautam , Rodig Scott. J. , Tian Ruiyang , Foley Kathleen M. , Bowman Teresa , Miron Alexander , Brown Myles , Iglehart J. Dirk. , Biswas Debajit K.
Published: April 2023

PDF file - 669K, Figure S1. FACS sorting of HER2-enriched fraction of SKBR3 and analysis of same by FACS in parental derivatives. Figure S2. Inhibition of HER2 signaling by Lapatinib in SKR6 and SKR6LR cells. Figure S3. Xenograft histopathology. Figure S4. NF-κB DNA binding activity by electrophoretic mobility shift assay (EMSA). Figure S5. Geno Ontology (GO) terms for genes found in clusters II, III and IV from Figure 5B. Figure S6. Hypothesis: Constitutive activation of NF-kB accelerates tumor growth by evading drug sensitivity resulting in poor clinical outcome.
Supplementary Figure 1 and Tables 1-2 from The Small Cell Lung Cancer-Specific Isoform of RE1-Silencing Transcription Factor (REST) Is Regulated By Neural-Specific Ser/Arg Repeat-Related Protein of 100 kDa (nSR100)
Authors: Shimojo Masahito , Shudo Yoshie , Ikeda Masatoshi , Kobashi Tomoyo , Ito Seiji
Published: April 2023

PDF - 202KB, Supplementary Figure 1: Growth curve for human SCLC cell lines growing on plastic or ECL extracellular matrix coated plastic dishes. Supplementary Table 1: Primers used for gene expression analysis. Supplementary Table 2: Comprehensive list of SCLC-associated autoantigens and autoantibodies.
Supplementary Figure Legend from RASSF1A-Mediated Regulation of AREG via the Hippo Pathway in Hepatocellular Carcinoma
Authors: Ahn Ei Yong , Kim Ji Su , Kim Gi Jeong , Park Young Nyun
Published: April 2023

PDF file - 86K
Supplementary Figure 3 from Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing
Authors: Hart Martin , Nolte Elke , Wach Sven , Szczyrba Jaroslaw , Taubert Helge , Rau Tilman T. , Hartmann Arndt , Grässer Friedrich A. , Wullich Bernd
Published: April 2023

PDF file - 123K, Analysis of miR-15a and miR-200b expression by Northern blotting (A) Ectopic expression of miR-15a and miR-200b. 293T cells were transfected either with pSG5 vector or with the pSG5-miR-15a or-200b expression plasmids. The ectopic expression of the miRNAs was detected by Northern blotting using specific radioactive labeled probes. (B) Endogenous expression of miR-15a and miR-200b in PCa cell lines DU145 and LNCaP. Total RNA was extracted from the cell lines PNF, DU145 and LNCaP and analyzed by Northern blotting using specific radioactive labeled probes against miR-15a and -200b. tRNA served as loading control.
Supplemental Table 10 from Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value
Authors: Meseure Didier , Vacher Sophie , Alsibai Kinan Drak , Nicolas Andre , Chemlali Walid , Caly Martial , Lidereau Rosette , Pasmant Eric , Callens Celine , Bieche Ivan
Published: April 2023

Relationship between ARF transcripts levels and classical clinical biological parameters in a series of 456 breast cancers.
Material and Methods from A Synthetic Lethal Screen Reveals Enhanced Sensitivity to ATR Inhibitor Treatment in Mantle Cell Lymphoma with ATM Loss-of-Function
Authors: Menezes Daniel L. , Holt Jenny , Tang Yan , Feng Jiajia , Barsanti Paul , Pan Yue , Ghoddusi Majid , Zhang Wei , Thomas George , Holash Jocelyn , Lees Emma , Taricani Lorena
Published: April 2023

Material and Methods
Supplementary table from Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression
Authors: Edwards Lauren , Gupta Rohit , Filipp Fabian Volker
Published: April 2023

SI_01_Patient_Cohort Patient barcodes and datasets of SKCM TCGA project SI_02_WES_DPYD Patient barcodes pf WES data and mutational status of DPYD SI_03_Clinical_Data Clinical data of pharmaceutical drugs and therapy types of patients in SKCM TCGA project SI_04_PYR_LOG2RNASEQ Log2 RNASEQ gene expression data of genes in pyrimidine pathway KEGG ID:00240 SI_05_PYR_MUTSIG Functional somatic mutations of genes in pyrimidine pathway KEGG ID:00240 in TCGA SKCM project SI_06_PAN_DPYD_MUTSIG Functional somatic mutations in DPYD in TCGA PAN-cancer project SI_07_Somatic_Mutations_DPYD Structural analysis of somatic mutations in DPYD in TCGA PAN-cancer project SI_08_DPYD_Melanoma_Progression Differences of Log2 RNASEQ gene expression between patients with WT and mutational status of DPYD in TCGA SKCM SI_09_Glossary and_GeneSymbols Glossary of Gene Symbols and NCBI Gene IDs of pyrimidine pathway and oncogenes identified SI_01-03 Pivot table organizing TCGA barcodes, utilized NGS and clinical data of SKCM cohort SI_04-05 Pivot table showing significant deregulation of gene expression and occurance of somatic mutations in pyrimidine pathway Average log2 RSEM RNASeq data is sorted by significant changes between metastatic (TM) and primary (TP) tumors NCBI Gene ID is used to catalogue genes; discrepancies between RNASeq transcript Gene Symbols and IDs are highlighted SI_06-08 Pivot table showing significance of somatic mutations in DPYD across Pan Cancer TCGA project Pivot table listing somatic mutations of DPYD, solvent accessible surface area, and functional impact by PPH2 Pivot table showing enrichment of pathway deregulation.
Supplemental Methods from Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal
Authors: Morris Van , Rao Xiayu , Pickering Curtis , Foo Wai Chin , Rashid Asif , Eterovic Karina , Kim Taebeom , Chen Ken , Wang Jing , Shaw Kenna , Eng Cathy
Published: April 2023

Genomic DNA: library prep and capture.
Table S2 from CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration
Authors: Wei Yuhong , Vellanki Ravi N. , Coyaud Étienne , Ignatchenko Vladimir , Li Lei , Krieger Jonathan R. , Taylor Paul , Tong Jiefei , Pham Nhu-An , Liu Geoffrey , Raught Brian , Wouters Bradly G. , Kislinger Thomas , Tsao Ming Sound , Moran Michael F.
Published: April 2023

Table S2. Transitions measured by SRM mass spectrometry
Supplementary Figures from Sonic Hedgehog Signaling Drives Mitochondrial Fragmentation by Suppressing Mitofusins in Cerebellar Granule Neuron Precursors and Medulloblastoma
Authors: Malhotra Anshu , Dey Abhinav , Prasad Niyathi , Kenney Anna Marie
Published: April 2023

Supplementary Figures
Supplementary Fig. S1 from Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells
Authors: Lambert Arthur W. , Wong Chen Khuan , Ozturk Sait , Papageorgis Panagiotis , Raghunathan Rekha , Alekseyev Yuriy , Gower Adam C. , Reinhard Björn M. , Abdolmaleky Hamid M. , Thiagalingam Sam
Published: April 2023

POSTN Expression if TGF-beta-dependent in M cells
Supplementary Movie 2 from O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors
Authors: Efimova Elena V. , Appelbe Oliver K. , Ricco Natalia , Lee Steve S.-Y. , Liu Yue , Wolfgeher Donald J. , Collins Tamica N. , Flor Amy C. , Ramamurthy Aishwarya , Warrington Sara , Bindokas Vytautas P. , Kron Stephen J.
Published: April 2023

Intratumoral IRIF imaging demonstrates similar patterns for GFP-IBD (green) and TagRFP-IBD (red) fluorescence in tumor at 3 h after irradiation with 6 Gy.Control tumor
Table S2:SIRT-1 siRNA sequence and gene location from Aromatase Acetylation Patterns and Altered Activity in Response to Sirtuin Inhibition
Authors: Molehin Deborah , Castro-Piedras Isabel , Sharma Monica , Sennoune Souad R. , Arena Daphne , Manna Pulak R. , Pruitt Kevin
Published: April 2023

Supplementary Table 2: siGENOME SMARTpool, Human SIRT1 siRNA sequence and exon location in the gene.
Supplementary Figure 7 from Inhibition of the ATR–CHK1 Pathway in Ewing Sarcoma Cells Causes DNA Damage and Apoptosis via the CDK2-Mediated Degradation of RRM2
Authors: Koppenhafer Stacia L. , Goss Kelli L. , Terry William W. , Gordon David J.
Published: April 2023

Supplementary Figure 7 shows cell cycle analysis for CDK1-AF cells and immunoblotting for P-Lamin A/C.
Supplementary Figure S1 from ABCC1-Exported Sphingosine-1-phosphate, Produced by Sphingosine Kinase 1, Shortens Survival of Mice and Patients with Breast Cancer
Authors: Yamada Akimitsu , Nagahashi Masayuki , Aoyagi Tomoyoshi , Huang Wei-Ching , Lima Santiago , Hait Nitai C. , Maiti Aparna , Kida Kumiko , Terracina Krista P. , Miyazaki Hiroshi , Ishikawa Takashi , Endo Itaru , Waters Michael R. , Qi Qianya , Yan Li , Milstien Sheldon , Spiegel Sarah , Takabe Kazuaki
Published: April 2023

Protein expression of ABCC1 in MCF7 with ABCC1 overexpression.
Table S5 from MCL1 and DEDD Promote Urothelial Carcinoma Progression
Authors: Hong Andrew L. , Guerriero Jennifer L. , Doshi Mihir B. , Kynnap Bryan D. , Kim Won Jun , Schinzel Anna C. , Modiste Rebecca , Schlauch Amy J. , Adam Rosalyn M. , Kwiatkowski David J. , Beroukhim Rameen , Letai Anthony , Rosenberg Jonathan E. , Hahn William C.
Published: April 2023

RIGER analyses of RNAi arrayed screen
Supplementary Figure S4 from Novel Oral mTORC1/2 Inhibitor TAK-228 Has Synergistic Antitumor Effects When Combined with Paclitaxel or PI3Kα Inhibitor TAK-117 in Preclinical Bladder Cancer Models
Authors: Hernández-Prat Anna , Rodriguez-Vida Alejo , Juanpere-Rodero Nuria , Arpi Oriol , Menéndez Silvia , Soria-Jiménez Luis , Martínez Alejandro , Iarchouk Natalia , Rojo Federico , Albanell Joan , Brake Rachael , Rovira Ana , Bellmunt Joaquim
Published: April 2023

Cellular effects of TAK-117 on human bladder cancer cell lines in vitro and in vivo.
Suppl. Figure Legends from PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors
Authors: Parsels Leslie A. , Karnak David , Parsels Joshua D. , Zhang Qiang , Vélez-Padilla Jonathan , Reichert Zachery R. , Wahl Daniel R. , Maybaum Jonathan , O'Connor Mark J. , Lawrence Theodore S. , Morgan Meredith A.
Published: April 2023

Suppl. Figure Legends
Supplementary Figure 2 from Radiation-Induced Malignant Transformation of Preneoplastic and Normal Breast Primary Epithelial Cells
Authors: Repullés Joan , Anglada Teresa , Soler David , Ramírez Juan Carlos , Genescà Anna , Terradas Mariona
Published: April 2023

BPEC culture characterisation
Supp. Figure 2 from Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic Glycolysis and Generation of Hyperpolarized [1-13C] Lactate
Authors: Tee Sui Seng , Suster Izabela , Truong Steven , Jeong Sangmoo , Eskandari Roozbeh , DiGialleonardo Valentina , Alvarez Julio A. , Aldeborgh Hannah N. , Keshari Kayvan R.
Published: April 2023

Western blot of metabolic proteins in LnCAP cells.
Legend to Supplemental Figures from Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1–EGFR Signaling in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells
Authors: Montanari Micaela , Carbone Maria Rita , Coppola Luigi , Giuliano Mario , Arpino Grazia , Lauria Rossella , Nardone Agostina , Leccia Felicia , Trivedi Meghana V. , Garbi Corrado , Bianco Roberto , Avvedimento Enrico V. , De Placido Sabino , Veneziani Bianca Maria
Published: April 2023

Legend to Supplemental Figures
Figure S5 from Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1–EGFR Signaling in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells
Authors: Montanari Micaela , Carbone Maria Rita , Coppola Luigi , Giuliano Mario , Arpino Grazia , Lauria Rossella , Nardone Agostina , Leccia Felicia , Trivedi Meghana V. , Garbi Corrado , Bianco Roberto , Avvedimento Enrico V. , De Placido Sabino , Veneziani Bianca Maria
Published: April 2023

Thy1 methylation in breast cancer
Supplemental Figures from BMP7 Signaling in TGFBR2-Deficient Stromal Cells Provokes Epithelial Carcinogenesis
Authors: Eikesdal Hans Petter , Becker Lisa M. , Teng Yingqi , Kizu Akane , Carstens Julienne L. , Kanasaki Keizo , Sugimoto Hikaru , LeBleu Valerie S. , Kalluri Raghu
Published: April 2023

Supplementary figure 1. (A) Immunolabeling for phosphorylated p63 (p-p63), CK5, CK20 and Ki67 in forestomach sections of approximately 6-week-old mice with the listed genotypes. Supplementary figure 2. Individual channels microscopy imaging for the data presented in Figure 2F. Supplementary figure 3. (A) RT-PCR electrophoretic product for the listed genes in the forestomach fibroblasts from approximately 6-week-old mice with the listed genotypes. Supplementary figure 4. Supplementary figure 5. Uncropped western blots
Figure S3 from Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1–EGFR Signaling in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells
Authors: Montanari Micaela , Carbone Maria Rita , Coppola Luigi , Giuliano Mario , Arpino Grazia , Lauria Rossella , Nardone Agostina , Leccia Felicia , Trivedi Meghana V. , Garbi Corrado , Bianco Roberto , Avvedimento Enrico V. , De Placido Sabino , Veneziani Bianca Maria
Published: April 2023

Strategy used to obtain Thy1-low cells and dot plot analysis of CD24 and CD44 expressed on the cell surface of Thy1-positive (K197) and Thy1-low (Topo9) cells. Thy1 expression on viable cells is represented as counts vs FITC signal.
Figure S2 from Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1–EGFR Signaling in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells
Authors: Montanari Micaela , Carbone Maria Rita , Coppola Luigi , Giuliano Mario , Arpino Grazia , Lauria Rossella , Nardone Agostina , Leccia Felicia , Trivedi Meghana V. , Garbi Corrado , Bianco Roberto , Avvedimento Enrico V. , De Placido Sabino , Veneziani Bianca Maria
Published: April 2023

Steps of isolation of Thy1-positive cells
Table S1, S2 from Synergistic Activity with NOTCH Inhibition and Androgen Ablation in ERG-Positive Prostate Cancer Cells
Authors: Mohamed Ahmed A. , Tan Shyh-Han , Xavier Charles P. , Katta Shilpa , Huang Wei , Ravindranath Lakshmi , Jamal Muhammad , Li Hua , Srivastava Meera , Srivatsan Eri S. , Sreenath Taduru L. , McLeod David G. , Srinivasan Alagarsamy , Petrovics Gyorgy , Dobi Albert , Srivastava Shiv
Published: April 2023

ERG binding sites on NOTCH1 and NOTCH2 promoters and primer sequences used to amplify these locations.
Figure S3 from YAP Tyrosine Phosphorylation and Nuclear Localization in Cholangiocarcinoma Cells Are Regulated by LCK and Independent of LATS Activity
Authors: Sugihara Takaaki , Werneburg Nathan W. , Hernandez Matthew C. , Yang Lin , Kabashima Ayano , Hirsova Petra , Yohanathan Lavanya , Sosa Carlos , Truty Mark J. , Vasmatzis George , Gores Gregory J. , Smoot Rory L.
Published: April 2023

Quantitative RT-PCR analysis of on-target effects of si-SFK knockdown cell lines.
Figure S2 from YAP Tyrosine Phosphorylation and Nuclear Localization in Cholangiocarcinoma Cells Are Regulated by LCK and Independent of LATS Activity
Authors: Sugihara Takaaki , Werneburg Nathan W. , Hernandez Matthew C. , Yang Lin , Kabashima Ayano , Hirsova Petra , Yohanathan Lavanya , Sosa Carlos , Truty Mark J. , Vasmatzis George , Gores Gregory J. , Smoot Rory L.
Published: April 2023

Evaluation of Abl kinase inhibitor KW-2449 demonstrating no effect on YAP subcellular localization and minimal effect on YAP tyrosine 357 phosphorylation.