Live Conference Coverage AACR 2020 in Real Time: Monday June 22, 2020 Mid Day Sessions
Reporter: Stephen J. Williams, PhD
This post will be UPDATED during the next two days with notes from recordings from other talks
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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.
Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research
The prestigious Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research was established in 1997 to annually recognize a scientist of international renown who has made a major scientific discovery in basic cancer research OR who has made significant contributions to translational cancer research; who continues to be active in cancer research and has a record of recent, noteworthy publications; and whose ongoing work holds promise for continued substantive contributions to progress in the field of cancer. For more information regarding the 2020 award recipient go to aacr.org/awards.
John E. Dick, Enzo Galligioni, David A Tuveson
- not every cancer cell equal in their Cancer Hallmarks
- how do we monitor and measure clonal dynamics
- Barnie Clarkson did pivotal work on this
- most cancer cells are post mitotic but minor populations of cells were dormant and survive chemotherapy
- only one cell is 1 in a million can regenerate and transplantable in mice and experiments with flow cytometry resolved the question of potency and repopulation of only small percentage of cells and undergo long term clonal population
- so instead of going to cell lines and using thousands of shRNA looked at clinical data and deconvoluted the genetic information (RNASeq data) to determine progenitor and mature populations (how much is stem and how much is mature populations)
- in leukemic patients they have seen massive expansion of a single stem cell population so only need one cell in AML if the stem cells have the mutational hits early on in their development
- finding the “seeds of relapse”: finding the small subpopulation of stem cells that will relapse
- they looked in BALL;; there are cells resistant to l-aspariginase, dexamethasone, and vincristine
- a lot of OXPHOS related genes (in DRIs) that may be the genes involved in this resistance
- it a wonderful note of acknowledgement he dedicated this award to all of his past and present trainees who were the ones, as he said, made this field into what it is and for taking it into directions none of them could forsee
Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
Experimental and Molecular Therapeutics, Drug Development, Cancer Chemistry
Chemistry to the Clinic: Part 1: Lead Optimization Case Studies in Cancer Drug Discovery
How can one continue to deliver innovative medicines to patients when biological targets are becoming ever scarcer and less amenable to therapeutic intervention? Are there sound strategies in place that can clear the path to targets previously considered “undruggable”? Recent advances in lead finding methods and novel technologies such as covalent screening and targeted protein degradation have enriched the toolbox at the disposal of drug discovery scientists to expand the druggable ta
Stefan N Gradl, Elena S Koltun, Scott D Edmondson, Matthew A. Marx, Joachim Rudolph
Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
Bioinformatics and Systems Biology, Molecular and Cellular Biology/Genetics
Informatics Technologies for Cancer Research
Cancer researchers are faced with a deluge of high-throughput data. Using these data to advance understanding of cancer biology and improve clinical outcomes increasingly requires effective use of computational and informatics tools. This session will introduce informatics resources that support the data management, analysis, visualization, and interpretation. The primary focus will be on high-throughput genomic data and imaging data. Participants will be introduced to fundamental concepts
Rachel Karchin, Daniel Marcus, Andriy Fedorov, Obi Lee Griffith
- Variant analysis is the big bottleneck, especially interpretation of variants
- CIVIC resource is a network for curation, interpretation of genetic variants
- CIVIC curators go through multiple rounds of editors review
- gene summaries, variant summaries
- curation follows ACSME guidelines
- evidences are accumulated, categories by various ontologies and is the heart of the reports
- as this is a network of curators the knowledgebase expands
- CIVIC is linked to multiple external informatic, clinical, and genetic databases
- they have curated 7017 clinical interpretations, 2527 variants, using 2578 papers, and over 1000 curators
- they are currently integrating with COSMIC ClinVar, and UniProt
- they are partnering with ClinGen to expand network of curators and their curation effort
- CIVIC uses a Python interface; available on website
The Precision Medicine Revolution
Precision medicine refers to the use of prevention and treatment strategies that are tailored to the unique features of each individual and their disease. In the context of cancer this might involve the identification of specific mutations shown to predict response to a targeted therapy. The biomedical literature describing these associations is large and growing rapidly. Currently these interpretations exist largely in private or encumbered databases resulting in extensive repetition of effort.
CIViC’s Role in Precision Medicine
Realizing precision medicine will require this information to be centralized, debated and interpreted for application in the clinic. CIViC is an open access, open source, community-driven web resource for Clinical Interpretation of Variants in Cancer. Our goal is to enable precision medicine by providing an educational forum for dissemination of knowledge and active discussion of the clinical significance of cancer genome alterations. For more details refer to the 2017 CIViC publication in Nature Genetics.
U24 funding announced: We are excited to announce that the Informatics Technology for Cancer Research (ICTR) program of the National Cancer Institute (NCI) has awarded funding to the CIViC team! Starting this year, a five-year, $3.7 million U24 award (CA237719), will support CIViC to develop Standardized and Genome-Wide Clinical Interpretation of Complex Genotypes for Cancer Precision Medicine.
Informatics tools for high-throughput analysis of cancer mutations
Rachel Karchin
- CRAVAT is a platform to determine, categorize, and curate cancer mutations and cancer related variants
- adding new tools used to be hard but having an open architecture allows for modular growth and easy integration of other tools
- so they are actively making an open network using social media
Towards FAIR data in cancer imaging research
Andriy Fedorov, PhD
Towards the FAIR principles
While LOD has had some uptake across the web, the number of databases using this protocol compared to the other technologies is still modest. But whether or not we use LOD, we do need to ensure that databases are designed specifically for the web and for reuse by humans and machines. To provide guidance for creating such databases independent of the technology used, the FAIR principles were issued through FORCE11: the Future of Research Communications and e-Scholarship. The FAIR principles put forth characteristics that contemporary data resources, tools, vocabularies and infrastructures should exhibit to assist discovery and reuse by third-parties through the web. Wilkinson et al.,2016. FAIR stands for: Findable, Accessible, Interoperable and Re-usable. The definition of FAIR is provided in Table 1:
| Number | Principle |
|---|---|
| F | Findable |
| F1 | (meta)data are assigned a globally unique and persistent identifier |
| F2 | data are described with rich metadata |
| F3 | metadata clearly and explicitly include the identifier of the data it describes |
| F4 | (meta)data are registered or indexed in a searchable resource |
| A | Accessible |
| A1 | (meta)data are retrievable by their identifier using a standardized communications protocol |
| A1.1 | the protocol is open, free, and universally implementable |
| A1.2 | the protocol allows for an authentication and authorization procedure, where necessary |
| A2 | metadata are accessible, even when the data are no longer available |
| I | Interoperable |
| I1 | (meta)data use a formal, accessible, shared, and broadly applicable language for knowledge representation. |
| I2 | (meta)data use vocabularies that follow FAIR principles |
| I3 | (meta)data include qualified references to other (meta)data |
| R | Reusable |
| R1 | meta(data) are richly described with a plurality of accurate and relevant attributes |
| R1.1 | (meta)data are released with a clear and accessible data usage license |
| R1.2 | (meta)data are associated with detailed provenance |
| R1.3 | (meta)data meet domain-relevant community standards |
A detailed explanation of each of these is included in the Wilkinson et al., 2016 article, and the Dutch Techcenter for Life Sciences has a set of excellent tutorials, so we won’t go into too much detail here.
- for outside vendors to access their data, vendors would need a signed Material Transfer Agreement but NCI had formulated a framework to facilitate sharing of data using a DIACOM standard for imaging data
Monday, June 22
1:30 PM – 3:01 PM EDT
Virtual Educational Session
Experimental and Molecular Therapeutics, Cancer Chemistry, Drug Development, Immunology
Engineering and Physical Sciences Approaches in Cancer Research, Diagnosis, and Therapy
The engineering and physical science disciplines have been increasingly involved in the development of new approaches to investigate, diagnose, and treat cancer. This session will address many of these efforts, including therapeutic methods such as improvements in drug delivery/targeting, new drugs and devices to effect immunomodulation and to synergize with immunotherapies, and intraoperative probes to improve surgical interventions. Imaging technologies and probes, sensors, and bioma
Claudia Fischbach, Ronit Satchi-Fainaro, Daniel A Heller
Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
Survivorship
Exceptional Responders and Long-Term Survivors
How should we think about exceptional and super responders to cancer therapy? What biologic insights might ensue from considering these cases? What are ways in which considering super responders may lead to misleading conclusions? What are the pros and cons of the quest to locate exceptional and super responders?
Alice P Chen, Vinay K Prasad, Celeste Leigh Pearce
Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
Tumor Biology, Immunology
Exploiting Metabolic Vulnerabilities in Cancer
The reprogramming of cellular metabolism is a hallmark feature observed across cancers. Contemporary research in this area has led to the discovery of tumor-specific metabolic mechanisms and illustrated ways that these can serve as selective, exploitable vulnerabilities. In this session, four international experts in tumor metabolism will discuss new findings concerning the rewiring of metabolic programs in cancer that support metabolic fitness, biosynthesis, redox balance, and the reg
Costas Andreas Lyssiotis, Gina M DeNicola, Ayelet Erez, Oliver Maddocks
Monday, June 22
1:30 PM – 3:30 PM EDT
Virtual Educational Session
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