Live Conference Coverage AACR 2020 in Real Time: Monday June 22, 2020 Late Day Sessions
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AACR VIRTUAL ANNUAL MEETING II
June 22-24: Free Registration for AACR Members, the Cancer Community, and the Public
This virtual meeting will feature more than 120 sessions and 4,000 e-posters, including sessions on cancer health disparities and the impact of COVID-19 on clinical trials
This Virtual Meeting is Part II of the AACR Annual Meeting. Part I was held online in April and was centered only on clinical findings. This Part II of the virtual meeting will contain all the Sessions and Abstracts pertaining to basic and translational cancer research as well as clinical trial findings.
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Virtual Educational Session
Prevention Research, Science Policy, Epidemiology, Survivorship
Carcinogens at Home: Science and Pathways to Prevention
Chemicals known to cause cancer are used and released to the environment in large volumes, exposing people where they live, work, play, and go to school. The science establishing an important role for such exposures in the development of cancers continues to strengthen, yet cancer prevention researchers are largely unfamiliar with the data drawn upon in identifying carcinogens and making decisions about their use. Characterizing and reducing harmful exposures and accelerating the devel
Julia Brody, Kathryn Z. Guyton, Polly J. Hoppin, Bill Walsh, Mary H. Ward
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Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
Tumor Biology, Molecular and Cellular Biology/Genetics, Clinical Research Excluding Trials
EMT Still Matters: Let’s Explore! – Dedicated to the Memory of Isaiah J. Fidler
During carcinoma progression, initially benign epithelial cells acquire the ability to invade locally and disseminate to distant tissues by activating epithelial-mesenchymal transition (EMT). EMT is a cellular process during which epithelial cells lose their epithelial features and acquire mesenchymal phenotypes and behavior. Growing evidence supports the notion that EMT programs during tumor progression are usually activated to various extents and often partial and reversible, thus pr
Jean-Paul Thiery, Heide L Ford, Jing Yang, Geert Berx
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Monday, June 22
1:30 PM – 3:00 PM EDT
Virtual Educational Session
Tumor Biology, Experimental and Molecular Therapeutics, Molecular and Cellular Biology/Genetics
One of These Things Is Not Like the Other: The Many Faces of Senescence in Cancer
Cellular senescence is a stable cell growth arrest that is broadly recognized to act as a barrier against tumorigenesis. Senescent cells acquire a senescence-associated secretory phenotype (SASP), a transcriptional response involving the secretion of inflammatory cytokines, immune modulators, and proteases that can shape the tumor microenvironment. The SASP can initially stimulate tumor immune surveillance and reinforce growth arrest. However, if senescent cells are not removed by the
Clemens A Schmitt, Andrea Alimonti, René Bernards
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Monday, June 22
1:30 PM – 3:00 PM EDT
Virtual Educational Session
Clinical Research Excluding Trials, Molecular and Cellular Biology/Genetics
Recent Advances in Applications of Cell-Free DNA
The focus of this educational session will be on recent developments in cell-free DNA (cfDNA) analysis that have the potential to impact the care of cancer patients. Tumors continually shed DNA into the circulation, where it can be detected as circulating tumor DNA (ctDNA). Analysis of ctDNA has become a routine part of care for a subset of patients with advanced malignancies. However, there are a number of exciting potential applications that have promising preliminary data but that h
Michael R Speicher, Maximilian Diehn, Aparna Parikh
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Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Methods Workshop
Clinical Research Excluding Trials, Clinical Trials, Experimental and Molecular Therapeutics, Molecular and Cellular Biology/Genetics
Translating Genetics and Genomics to the Clinic and Population
This session will describe how advances in understanding cancer genomes and in genetic testing technologies are being translated to the clinic. The speakers will illustrate the clinical impact of genomic discoveries for diagnostics and treatment of common tumor types in adults and in children. Cutting-edge technologies for characterization of patient and tumor genomes will be described. New insights into the importance of patient factors for cancer risk and outcome, including predispos
Heather L. Hampel, Gordana Raca, Jaclyn Biegel, Jeffrey M Trent
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Monday, June 22
1:30 PM – 3:22 PM EDT
Virtual Educational Session
Regulatory Science and Policy, Drug Development, Epidemiology
Under-representation in Clinical Trials and the Implications for Drug Development
The U.S. Food and Drug Administration relies on data from clinical trials to determine whether medical products are safe and effective. Ideally, patients enrolled in those trials are representative of the population in which the product will be used if approved, including people of different ages, races, ethnic groups, and genders. Unfortunately, with few patients enrolling in clinical trials, many groups are not well-represented in clinical trials. This session will explore challenges
Ajay K. Nooka, Nicole J. Gormley, Kenneth C Anderson, Ruben A. Mesa, Daniel J. George, Yelak Biru, RADM Richardae Araojo, Lola A. Fashoyin-Aje
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Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Cancer Chemistry
Targeted Protein Degradation: Target Validation Tools and Therapeutic Opportunity
This educational session will cover the exciting emerging field of targeted protein degradation. Key learning topics will include: 1. an introduction to the technology and its relevance to oncology; 2. PROTACS, degraders, and CELMoDs; 3. enzymology and protein-protein interactions in targeted protein degraders; 4. examples of differentiated biology due to degradation vs. inhibition; 5. how to address questions of specificity; and 6. how the field is approaching challenges in optimizing therapies
George Burslem, Mary Matyskiela, Lyn H. Jones, Stewart L Fisher, Andrew J Phillips
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Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Bioinformatics and Systems Biology, Experimental and Molecular Therapeutics, Drug Development, Molecular and Cellular Biology/Genetics
Obstacles and opportunities for protein degradation drug discovery
Lyn H. Jones
- PROTACs ubiquitin mediated by E3 ligases; first discovered by DeShaies and targeted to specific proteins
- PROTACs used in drug discovery against a host of types of targets including kinases and membrane receptors
- PROTACs can be modular but lack molecular structural activity relationships
- can use chemical probes for target validation
- four requirements: candidate exposure at site of action (for example lipophilicity for candidates needed to cross membranes and accumulate in lysosomes), target engagement (ternary occupancy as measured by FRET), functional pharmacology, relevant phenotype
- PROTACs hijack the proteosomal degradation system
Proteolysis-targeting chimeras as therapeutics and tools for biological discovery
George Burslem
- first PROTAC developed to coopt the VHL ubiquitin ligase system which degrades HIF1alpha but now modified for EREalpha
- in screen for potential PROTACS there were compounds which bound high affinity but no degradation so phenotypic screening very important
- when look at molecular dynamics can see where PROTAC can add additional protein protein interaction, verifed by site directed mutagenesis
- able to target bcr-Abl
- he says this is a rapidly expanding field because of all the new E3 ligase targets being discovered
Expanding the horizons of cereblon modulators
Mary Matyskiela
Translating cellular targeted protein degradation to in vivo models using an enzymology framework
Stewart L Fisher
- new targeting compounds have an E3 ligase binding domain, a target binding domain and a linker domain
- in vivo these compounds are very effective; BRD4 degraders good invitro and in vivo with little effect on body weight
- degraders are essential activators of E3 ligases as these degraders bring targets in close proximity so activates a catalytic cycle of a multistep process (has now high turnover number)
- in enzymatic pathway the degraders make a productive complex so instead of a kcat think of measuring a kprod or productivity of degraders linked up an E3 ligase
- the degraders are also affecting the rebound protein synthesis; so Emax never to zero and see a small rebound of protein synthesis
Data-Driven Approaches for Choosing Combinatorial Therapies
Drug combinations remain the gold standard for treating cancer, as they significantly outperform single agents. However, due to the enormous size of drug combination space, it is virtually impossible to interrogate all possible combinations. This session will discuss approaches to identify novel combinations using both experimental and computational approaches. Speakers will discuss i) approaches to drug screening in cell lines, the impact of the microenvironment, and attempts to more
Bence Szalai, James E Korkola, Lisa Tucker-Kellogg, Jeffrey W Tyner
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Monday, June 22
3:45 PM – 5:21 PM EDT
Virtual Educational Session
Tumor Biology
Cancer Stem Cells and Therapeutic Resistance
Cancer stem cells are a subpopulation of cells with a high capacity for self-renewal, differentiation and resistance to therapy. In this session, we will define cancer stem cells, discuss cellular plasticity, interactions between cancer stem cells and the tumor microenvironment, and mechanisms that contribute to therapeutic resistance.
Robert S Kerbel, Dolores Hambardzumyan, Jennifer S. Yu
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Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Drug Development, Experimental and Molecular Therapeutics
Molecular Imaging in Cancer Research
This session will cover the fundamentals as well as the major advances made in the field of molecular imaging. Topics covered will include the basics for optical, nuclear, and ultrasound imaging; the pros and cons of each modality; and the recent translational advancements. Learning objectives include the fundamentals of each imaging modality, recent advances in the technology, the processes involved to translate an imaging agent from bench to bedside, and how molecular imaging can gui
Julie Sutcliffe, Summer L Gibbs, Mark D Pagel, Katherine W Ferrara
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Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Tumor Biology, Immunology, Experimental and Molecular Therapeutics, Drug Development
Tumor Endothelium: The Gatekeepers of Tumor Immune Surveillance
Tumor-associated endothelium is a gatekeeper that coordinates the entry and egress of innate and adaptive immune cells within the tumor microenvironment. This is achieved, in part, via the coordinated expression of chemokines and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. Crosstalk between adaptive immune cells and the tumor endothelium is therefore essential for tumor immune surveillance and the success of immune-based thera
Dai Fukumura, Maria M Steele, Wen Jiang, Andrew C Dudley
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Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Immunology, Experimental and Molecular Therapeutics
Novel Strategies in Cancer Immunotherapy: The Next Generation of Targets for Anticancer Immunotherapy
T-cell immunotherapy in the form of immune checkpoint blockade or cellular T-cell therapies has been tremendously successful in some types of cancer. This success has opened the door to consider what other modalities or types of immune cells can be harnessed for exert antitumor functions. In this session, experts in their respective fields will discuss topics including novel approaches in immunotherapy, including NK cells, macrophage, and viral oncotherapies.
Evanthia Galanis, Kerry S Campbell, Milan G Chheda, Jennifer L Guerriero
DETAILS
Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Tumor Biology, Drug Development, Immunology, Clinical Research Excluding Trials
Benign Cells as Drivers of Cancer Progression: Fat and Beyond
Carcinomas develop metastases and resistance to therapy as a result of interaction with tumor microenvironment, composed of various nonmalignant cell types. Understanding the complexity and origins of tumor stromal cells is a prerequisite for development of effective treatments. The link between obesity and cancer progression has revealed the engagement of adipose stromal cells (ASC) and adipocytes from adjacent fat tissue. However, the molecular mechanisms through which they stimulate
Guojun Wu, Matteo Ligorio, Mikhail Kolonin, Maria T Diaz-Meco
DETAILS
Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Educational Session
Clinical Research Excluding Trials, Experimental and Molecular Therapeutics, Tumor Biology
Dharma Master Jiantai Symposium on Lung Cancer: Know Thy Organ – Lessons Learned from Lung and Pancreatic Cancer Research
The term “cancer” encompasses hundreds of distinct disease entities involving almost every possible site in the human body. Effectively interrogating cancer, either in animals models or human specimens, requires a deep understanding of the involved organ. This includes both the normal cellular constituents of the affected tissue as well as unique aspects of tissue-specific tumorigenesis. It is critical to “Know Thy Organ” when studying cancer. This session will focus on two of the most
Trudy G Oliver, Hossein Borghaei, Laura Delong Wood, Howard C Crawford
DETAILS
Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Methods Workshop
Clinical Trials
Clinical Trial Design: Part 1: Novel Approaches and Methods in Clinical Trial Design
Good clinical trial design has always had to balance the competing interests of effectively and convincingly answering the question with the limitations imposed by scarce resources, complex logistics, and risks and potential benefits to participants. New targeted therapies, immuno-oncology, and novel combination treatments add new challenges on top of the old ones. This session will introduce these concerns and 1) suggest ways to consider what outcomes are relevant, 2) how we can best
Mary W. Redman, Nolan A. Wages, Susan G Hilsenbeck, Karyn A. Goodman
DETAILS
Monday, June 22
3:45 PM – 5:45 PM EDT
Virtual Methods Workshop
Tumor Biology, Drug Development
High-Throughput Screens for Drivers of Progression and Resistance
The sequencing of human cancers now provides a landscape of the genetic alterations that occur in human cancer, and increasingly knowledge of somatic genetic alterations is becoming part of the evaluation of cancer patients. In some cases, this information leads directly to the selection of particular therapeutic approaches; however, we still lack the ability to decipher the significance of genetic alterations in many cancers. This session will focus on recent developments that permit the identification of molecular targets in specific cancers. This information, coupled with genomic characterization of cancer, will facilitate the development of new therapeutic agents and provide a path to implement precision cancer medicine to all patients.
William C Hahn, Mark A Dawson, Mariella Filbin, Michael Bassik
DETAILS
Monday, June 22
3:45 PM – 5:15 PM EDT
Defining a cancer dependency map
William C Hahn
Introduction
William C Hahn
Genome-scale CRISPR screens in 3D spheroids identify cancer vulnerabilities
Michael Bassik
Utilizing single-cell RNAseq and CRISPR screens to target cancer stem cells in pediatric brain tumors
Mariella Filbin
- many gliomas are defined by discreet mutational spectra that also discriminates based on age and site as well (for example many cortical tumors have mainly V600E Braf mutations while thalamus will be FGFR1
- they did single cell RNAseq on needle biopsy from 7 gliomas which gave about 3500 high quality single cells; obtained full length RNA
- tumors clustered mainly where the patient it came from but had stromal cell contamination probably so did a deconvolution? Copy number variation showed which were tumor cells and did principle component analysis
- it seems they used a human glioma model as training set
- identified a stem cell like glioma cell so concentrated on the genes altered in these for translational studies
- developed multiple PDX models from patients
- PDX transcriptome closest to patient transcriptome but organoid grown in serum free very close while organoids grown in serum very distinct transcriptome
- developed a CRISPR barcoded library to determine genes for survival genes
- pulled out BMI1 and EZH2 (polycomb complex proteins) as good targets
Virtual Methods Workshop
Prevention Research, Survivorship, Clinical Research Excluding Trials, Epidemiology
Implementation Science Methods for Cancer Prevention and Control in Diverse Populations: Integration of Implementation Science Methods in Care Settings
Through this Education Session we will use examples from ongoing research to provide an overview of implementation science approaches to cancer prevention and control research. We draw on examples to highlight study design approaches, research methods, and real-world solutions when applying implementation science to achieve health equity. Approaches to defining change in the care setting and measuring sustained changes are also emphasized. Using real examples of patient navigation prog
Graham A Colditz, Sanja Percac-Lima, Nathalie Huguet
DETAILS
Monday, June 22
3:45 PM – 5:30 PM EDT
Virtual Educational Session
Regulatory Science and Policy, Epidemiology
COVID-19 and Cancer: Guidance for Clinical Trial Conduct and Considerations for RWE
This session will consider the use of real-world evidence in the context of oncology clinical trials affected by the COVID-19 pandemic. Key aspects of the FDA’s recent “Guidance on Conduct of Clinical Trials of Medical Products of Medical Products during COVID-19 Public Health Emergency” will be discussed, including telemedicine, accounting for missing data, obtaining laboratory tests and images locally, using remote informed consent procedures, and additional considerations for contin
Wendy Rubinstein, Paul G. Kluetz, Amy P. Abernethy, Jonathan Hirsch, C.K. Wang
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