bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA02: Advances in drug delivery
Authors: Langer Robert S. 
Published: March 2017

Abstract
Advanced drug delivery systems are having an enormous impact on human health. We start by discussing our early research on developing the first controlled release systems for macromolecules and the isolation of angiogenesis inhibitors and how these led to numerous new cancer therapies. New drug delivery technologies including nanoparticles and nanotechnology are now being studied for use treating cancer and other illnesses. We will also discuss novel super long acting oral drug delivery systems as well as ways of developing novel microchips for drug delivery and how they also can be used for designing personalized cancer drug regimens. Finally, we will discuss new approaches for cell therapy based on a novel method of “squeezing” materials into cells.
Citation Format: Robert S. Langer. Advances in drug delivery. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA02.
Abstract IA04: Game theory and personalized cancer treatment
Authors: Austin Robert H. 
Published: March 2017

Abstract
The presence of driver mutations and subsequent clonal expansion by Darwinian evolution does not explain dormancy and re-emergence of cancer from a community of cancer and host cells (including stromal and immune cells). Dormancy appears to be a slow-driven, interaction-dominated, threshold system which is poorly prognosed. At the simplest level, we view cancer cells interacting with host cells via complex, non-linear population dynamics, which can lead to very non-intuitive but perhaps deterministic and understandable progression dynamics of cancer. We explore here the dynamics of host-cancer cell populations in the presence of (1) payoffs gradients and (2) perturbation due to cell migration to determine to what extent the time-dependence of the populations can be quantitatively understood in spite of the underlying complexity of the individual agents. The population dynamics presented here provide a model system for the clinic to map the payoffs matrices and suggest new avenues to predict drug dosages.
Citation Format: Robert H. Austin. Game theory and personalized cancer treatment. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA04.
Abstract IA13: Imaging drug delivery and nanotherapeutics
Authors: Weissleder Ralph 
Published: March 2017

Abstract
Over 180 chemically distinct cancer drugs are currently in clinical use while new nanomaterials, small molecule inhibitors and newer immunotherapeutics are entering clinical trials. Preclinical testing usually involves measuring tumor sizes, survival endpoints, the use of histopathology and measurement of serum biomarkers. Yet, despite all of these advances, preciously little is known on how many of these compounds actually work (or fail) at the single cell level in vivo, what the spatial and temporal heterogeneity is and how efficacy can be improved. The latter is particularly vexing as the majority of patients show suboptimal responses and tumors often relapse within months-years. With the recent development of i) single cell in vivo imaging technology (Nat Commun 2013;4,1504), ii) fluorescent nanoparticles and encapsulated therapeutics (Science Transl Med, 2015;7:314; Nat Commun. 2015;6:8692), iii) in vivo reporters of host response, cell death or DNA damage (ChemMedChem, 2014;9:1131), iv) new computational analysis (Nat Methods, 2015;12:577), and v) armed with new biological insight from feasibility studies we are now able to address important cancer therapeutics questions in ways that were not previously possible. In this presentation I will review imaging approaches for the functional assessment of new therapeutics at the single cell level in vivo, addressing key questions on distribution (pharmacokinetics, PK) and specific cellular response (pharmacodynamics, PD).
Citation Format: Ralph Weissleder. Imaging drug delivery and nanotherapeutics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA13.
Abstract IA14: Imaging tumor metabolism with hyperpolarized 13C-labeled cell substrates
Authors: Brindle Kevin M. 
Published: March 2017

Abstract
Molecular imaging can play an important role in predicting and detecting tumor responses to treatment and thus in guiding treatment in individual patients [1]. Nuclear spin hyperpolarization can increase sensitivity in the magnetic resonance experiment by &gt;10,000x. This has allowed imaging of injected hyperpolarized 13C labelled cell substrates in vivo and, more importantly, their metabolic conversion into other metabolites. We have been using this metabolic imaging technique both to detect treatment response and to investigate the tumor microenvironment. A recent perspective on this field of research is given in [2]. Exchange of hyperpolarized 13C label between lactate and pyruvate and net flux of label between glucose and lactate have been shown to decrease post-treatment and hyperpolarized [1,4-13C]fumarate has been shown to detect subsequent cell necrosis. Tumor pH can be imaged using hyperpolarized H13CO3- and redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively. In this talk I will discuss more recent work in which we have used hyperpolarized [1-13C]pyruvate to investigate metabolism in PDX models of glioblastoma. These measurements have shown significant heterogeneity between tumors derived from different patients, which we believe is related to underlying oncogenic mutations. I will also show how hyperpolarized [1-13C]pyruvate can be used to follow the progression of pancreatic precursor lesions, in a genetically engineered mouse model of the disease, which potentially could be used clinically to guide earlier intervention [3]. Finally I will discuss how we have used hyperpolarized [U-2H, U-13C]glucose [4] to investigate flux in the pentose phosphate pathway (PPP) and the relationship between PPP flux and the rate of reduction of hyperpolarized [1-13C]dehydroascorbate.
Metabolic imaging with hyperpolarized 13C-labelled cell substrates has recently translated to the clinic with a study in prostate cancer [5] and we have conducted our first clinical study in Cambridge using this technique earlier this year.
1. Brindle, K. Nature Rev Cancer 8, 94-107 (2008).
2. Brindle, K.M. J. Amer. Chem. Soc. 137, 6418-6427 (2015).
3. Serrao, E.M., et al. Gut 65, 465-475 (2016).
4. Rodrigues, T.B., et al. Nat Med 20, 93-97 (2014).
5. Nelson, S.J., et al. Science Translational Medicine 5, 198ra108 (2013).
Citation Format: Kevin M. Brindle. Imaging tumor metabolism with hyperpolarized 13C-labeled cell substrates. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA14.
Abstract IA22: Non-coding RNA from discovery to therapy
Authors: Sharp Phillip 
Published: March 2017

Abstract
The central roles of non-coding RNAs in both normal and malignant cells offer new approaches to detection and treatment of cancer. Changes in microRNA levels have illuminated epigenetic processes that appear to maintain an embryonic malignant state in some adult cancer cells. This epigenetic network involves a small set of oncofetal genes, also expressed in early embryos, conferring malignant properties. This same set is also part of a larger network that integrates nutrient level data according to the size of the vertebrates where it is found. Further, the existence of the biosynthetic pathway for microRNAs in all adult cells allows introduction of small interfering RNAs to silence genes. This is now highly effective for silencing genes in the liver of patients and may become a general new therapeutic modality. Finally, many long non-coding RNAs are synthetized from promoters and enhancers by divergent transcription. The importance of these non-coding RNAs in regulation of nearby genes is being investigated but there is no question that enhancers stimulate promoters through processes involving the action of RNA polymerase. It is critical to understand the mechanism of enhancer action because many new drug agents preferentially target super-enhancer associated genes. This type of enhancer is frequently associated with oncogenes in cancer cells.
Citation Format: Phillip Sharp. Non-coding RNA from discovery to therapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA22.
Abstract PR05: Glycoprotein-mediated tissue mechanics regulate glioblastoma aggression
Authors: Barnes J. Matthew , Woods Elliot C. , Bainer Russell O. , Miroshnikova Yekaterina A. , Lu Kan , Bergers Gabriele , Bertozzi Carolyn , Weaver Valerie M. 
Published: March 2017

Abstract
Glioblastoma multiforme (GBM) is a malignant glioma whose progression is associated with rampant extracellular matrix (ECM) remodeling. We recently found that GBM ECM stiffness predicts reduced survival in human patients. Instead of collagen fibrosis, which is common in many solid tumors, we showed that GBM stiffening involves increased production of extracellular glycoproteins, glycosaminoglycans, and sugar-binding proteins. Using bioinformatics, we revealed that genes of the glycocalyx (transmembrane glycoproteins and their interacting partners) are disproportionately upregulated in GBM relative to lower grade gliomas. Further, these genes are overexpressed within GBM in the mesenchymal (MES) relative to the proneural (PRO) subtype, the former of which is associated with treatment resistance and relapse. Using mouse models of human GBM, we showed that MES tumors are more lethal than PRO, and present with elevated ECM stiffness and mechanical signaling. To test our hypothesis that mechanical signaling can drive the MES phenotype, we engineered PRO GBM cells with constitutively-elevated integrin signaling. Compared to control PRO cells, these undergo a robust MES-like transition, upregulate bulky glycoprotein expression, and result in stiffer and more lethal tumors. This phenotype was reversed by the inhibition of focal adhesion kinase in MES cells. To test whether an enhanced glycocalyx can directly elevate mechanical signaling, we decorated GBM cells with synthetic glycoprotein polymers. Indeed, this resulted in enhanced integrin-focal adhesion signaling and more aggressive tumor progression. The invasive properties and therapy resistance observed in mesenchymal tumor cells are often associated with elevated stem cell-like features. To investigate a link between the glycocalyx, tissue mechanics, and the mesenchymal-stem cell phenotype, we interfered with components of the gylcocalyx or mechanical signaling machinery and found a reduction in stem cell genes and surface proteins, as well as increased sensitivity to chemotherapy. These data support a model in which glycoprotein-mediated tissue stiffening drives GBM aggression through promotion of a mesenchymal phenotype.
This abstract is also being presented as Poster A39.
Citation Format: J. Matthew Barnes, Elliot C. Woods, Russell O. Bainer, Yekaterina A. Miroshnikova, Kan Lu, Gabriele Bergers, Carolyn Bertozzi, Valerie M. Weaver. Glycoprotein-mediated tissue mechanics regulate glioblastoma aggression. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr PR05.
Abstract PR07: A biosensor mouse to predict the dissociation and spread of pancreatic cancer
Authors: Herrmann David , Erami Zahra , Warren Sean , Nobis Max , Magenau Astrid , Lucas Morghan , Vennin Claire , McGhee Ewan J. , Leung Wilfred , Reischmann Nadine , Mrowinska Agata , Schwarz Juliane P. , Kadir Shereen , Karim Saadia A. , Campbell Andrew D. , Gallego-Ortega David , Evans Jeffry , Sansom Owen J. , Morton Jennifer P. , Anderson Kurt I. , Timpson Paul 
Published: March 2017

Abstract
E-cadherin-mediated cell-cell junctions play a physical role in maintaining normal epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here, we have generated an E-cadherin-GFP(FRAP) biosensor mouse, which enables intravital photobleaching and quantification of E-cadherin mobility in live tissue, without affecting normal biology. We demonstrate using FRAP or FLIP, the broad applications of this mouse to examine E-cadherin regulation in multiple tissues including mammary, brain, liver and kidney, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue, upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment, and reveal new insights into the dynamic remodeling of E-cadherin during in situ cancer progression. Photobleaching in the E-cadherin-GFP(FRAP) mouse correlate directly with epithelial integrity and mechanical strength making the biosensor mouse a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native micro-environments.
This abstract is also being presented as Poster B23.
Citation Format: David Herrmann, Zahra Erami, Sean Warren, Max Nobis, Astrid Magenau, Morghan Lucas, Claire Vennin, Ewan J. McGhee, Wilfred Leung, Nadine Reischmann, Agata Mrowinska, Juliane P. Schwarz, Shereen Kadir, Saadia A. Karim, Andrew D. Campbell, David Gallego-Ortega, Jeffry Evans, Owen J. Sansom, Jennifer P. Morton, Kurt I. Anderson, Paul Timpson. A biosensor mouse to predict the dissociation and spread of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr PR07.
Abstract BS1-2: Epigenetic targets in breast cancer
Authors: Polyak K 
Published: March 2017

Abstract
Epigenetic regulators are emerging therapeutic targets in various human cancer types including breast cancer. Histone modification (e.g., methylation and acetylation) regulates chromatin structure and transcription, and abnormalities in this process lead to perturbed development and differentiation. Similarly, DNA methylation patterns are commonly perturbed in tumors and this can increase genetic instability and also cellular heterogeneity within tumors. The demonstration of frequent somatic mutations in histones and epigenetic regulators factors in a wide range of human cancer types underscores the importance of epigenetic regulation in tumorigenesis. In breast cancer, genes encoding transcriptional regulators (e.g., FOXA1, GATA3) are among the most frequently mutated genes, suggesting a key role for perturbed epigenetic programs in tumorigenesis. Epigenetic regulators are broadly categorized into writers – enzymes that catalyze the placement of modifications in histones or DNA such as histone and DNA methyltransferases, erasers – enzymes that remove histone or DNA modifications including histone and DNA demethylases, and readers – proteins that recognize a specific histone or DNA modification to help concentrate an enzymatic or structural protein complex. BET bromodomain family of chromatin regulators (e.g., BRD4) recognize acetylated histones and play a key role in the assembly of active transcription complexes. Targeting of these proteins by BET bromodomain inhibitors (BBDIs) have been shown to inhibit the growth of several cancer types and they appear promising novel therapeutic agents in breast cancer as well. However, a significant fraction of breast cancer cells is not sensitive to BBDIs and even some of the initial responsive ones relatively quickly acquire resistance due to activation of anti-apoptotic pathways and bromodomain-independent recruitment of BRD4 to the chromatin. Thus, inhibitors of BET bromodomain proteins alone or in combination with other compounds provide a promising novel therapeutic strategy for the treatment of breast tumors.
Citation Format: Polyak K. Epigenetic targets in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr BS1-2.
Abstract DL-1: Targeting breast cancer stem cells: Challenges and opportunities
Authors: Wicha MS 
Published: March 2017

Abstract
Breast cancers contain cell populations that display hierarchical organization at the apex of which are cells that display stem cell properties. These cancer stem cells (CSCs) mediate metastasis and contribute to treatment resistance. CSC's display cellular plasticity , a property that allows them to transition between mesenchymal and epithelial states, facilitating metastasis. Although different therapeutic strategies have been developed for the treatment of the various molecular subtypes of breast cancer, CSCs driving these cancers may share common regulatory pathways including those maintaining cellular plasticity. This suggests that therapeutic strategies targeting these CSC pathways may be complementary to subtype specific therapeutic agents targeting bulk cell populations. Furthermore, since CSCs constitute a minor fraction of total tumor cell populations classical clinical endpoints such as tumor regression are inadequate to assess the efficacy of CSC targeting therapeutics. Neoadjuvant trial designs allow for the direct assessment of treatment on biological targets and as well as the therapeutic effectiveness of CSC targeting agents. Molecular analysis of circulating tumor cells at single cell resolution provides an alternative method of accessing the effects of CSC targeting therapies.
CSCs are regulated by the tumor micro environment and recent studies suggest that the immune microenvironment plays a crucial role in CSC regulation. Immunotherapeutic approaches may provide a means to target heterogeneous CSC's as well as bulk tumor populations. Early phase clinical trials currently in progress have demonstrated the safety of CSC targeting agents. Future randomized trials will be required to determine whether addition of CSC targeting therapeutics to current agents targeting bulk cell populations improves the efficacy of these therapeutic agents.
Citation Format: Wicha MS. Targeting breast cancer stem cells: Challenges and opportunities [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr DL-1.
Abstract ES1-2: Paracrine signaling and intratumoral heterogeneity
Authors: Rosen JM 
Published: March 2017

Abstract
Breast cancer is no longer considered a single disease, but instead comprises multiple subtypes with genetically and most likely epigenetically heterogeneous tumors composed of numerous clones. Both the hierarchical cancer stem cell (CSC) and clonal evolution models have been invoked to help explain this intratumoral heterogeneity. Several recent studies have helped define the functional interactions among the different cellular subpopulations necessary for the evolution of this complex ecosystem. These interactions involve paracrine interactions that include locally acting Wnt family members, reminiscent of the signaling pathways important for normal mammary gland development and stem cell self-renewal. In addition, they involve interactions between breast cancer cells and the immune microenvironment. In this presentation, we will discuss the interactions among various cell populations in both normal and tumor tissues. A better understanding of these interactions, especially in the metastatic setting, will be important for the development of improved combinatorial therapies designed to prevent relapse and to ultimately decrease mortality.
Citation Format: Rosen JM. Paracrine signaling and intratumoral heterogeneity [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES1-2.
Abstract ES4-1: Basic science of immunotherapy
Authors: Knutson KL 
Published: March 2017

Abstract
While it remains unclear whether the immune system naturally evolved to prevent cancer, it is clear that many of its constituent cells and factors can greatly influence the clinical course of the disease in many different cancers, including breast cancer. Generally speaking, the immune system is a double edged sword and produces a broad array of both pro-tumor and anti-tumor factors. Of those which demonstrate anti-tumor activity, antigen-specific T cells (including both cytotoxic and helper T cells) are the most important as several studies have now shown that increased T cell infiltration is generally, and markedly, protective. More recent evidence also suggests that B cells can also be protective, particularly when producing tumor-specific antibodies or associated with intratumoral tertiary lymphoid structures. Thus, newer therapeutics being developed in academia and industry are being designed to directly augment adaptive immunity. The methods to manipulate the numbers of lymphocytes is growing and includes direct clonal expansion approaches such as vaccination and adoptive T cell therapy as well as more indirect methods that modulate cell intrinsic regulatory mechanisms (e.g. checkpoint and co-stimulatory pathways). In contrast, the pro-tumor activity of the immune system is largely mediated by the myeloid compartment of the immune system. While normal myeloid cells are not generally pro-tumorigenic, most tumors impair proper myeloid differentiation inducing intratumoral and systemic accumulation of defective myeloid cells which have profound tumor-promoting activity. This tumor-promoting activity of myeloid cells is mediated either through direct tumor growth-promoting activity (e.g. growth and angiogenic factors) or through blockade of adaptive immune response. Mechanisms by myeloid cells promote tumor growth appear to be diversified and are now only recently becoming understood, but nonetheless represent unique targets for therapeutic manipulation either alone in combination with other therapeutic modalities (e.g. checkpoint blockade). The basic underpinnings of tumor immunology are being rapidly identified and applied clinically to treat a variety of cancers and more recently breast cancer. This educational lecture will be a general overview of tumor immunology focusing on recent basic and therapeutic advances, highlighting those relevant to the field of breast cancer.
Citation Format: Knutson KL. Basic science of immunotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES4-1.