The American Association for Cancer Research (AACR) Annual Meeting is one of the most anticipated events in the field of oncology, bringing together researchers, clinicians, industry professionals, and advocates to share groundbreaking discoveries and advancements in cancer research. The theme of the AACR Annual Meeting 2024, “Inspiring Science, Fueling Progress, Revolutionizing Care,” sets the tone for an event focused on driving transformative change in cancer research and patient outcomes. According to the conference chairs, this year’s theme underscores the pivotal role of scientific inspiration in propelling progress and innovation across the cancer care continuum.

In line with the theme of innovation, several hot topics are expected to take center stage at the AACR Annual Meeting 2024. Data science, artificial intelligence (AI), and technology will feature prominently in discussions, reflecting the growing importance of leveraging advanced computational methods to accelerate cancer research and improve patient outcomes. Sessions dedicated to these topics will explore how data-driven approaches are reshaping our understanding of cancer biology, facilitating precision medicine initiatives, and driving the development of novel therapeutics.

Among the myriad of abstracts to be presented at the AACR Annual Meeting 2024, those focusing on spatial biology and the tumor microenvironment are generating significant interest. Spatial biology, a burgeoning field within cancer research, investigates the spatial organization of cells and biomolecules within tissues, offering insights into tumor heterogeneity, immune cell interactions, and therapeutic responses. Abstracts highlighting advances in spatial profiling technologies, imaging modalities, and computational analyses promise to deepen our understanding of the complex interplay between tumor cells and their microenvironment. The opening talk for AACR will be given by the new President of AACR, Philip Greenberg.

On Friday, April 5th, there will be a session titled “Single Cell Analysis for Bench-based Scientists”. This workshop aims to equip bench-based and clinical scientists with the latest analysis methods for interpreting data, extracting insights, and applying biological intuition while avoiding common misconceptions. It provides guidance on analyzing single-cell RNA sequencing data, covering state-of-the-art methods, best practices for normalization, visualization, clustering, and cell typing, with all workshop code freely available for adaptation. Roshan Sharma, from the Memorial Sloan Kettering Cancer Center, will discuss best practices for pre-processing of single-cell RNA-seq data. After Roshan’s talk, Orr Ashenberg, from the Broad Institute, will discuss how their group clusters and interprets single-cell RNA-seq data. Their lab developed a systematic toolbox for fresh and frozen tumor processing for both scRNA-Seq and snRNA-Seq. Their toolbox includes experimental workflow and methods, computational pipelines and evaluation metrics. To validate their toolbox, they tested eight different tumor types, each with unique tissue characteristics. Their computational pipelines can be found at https://github.com/klarman-cell-observatory/HTAPP-Pipelines. Details of their findings will be presented.

On Saturday, April 6 there will be a session on the Lineage Plasticity in Tumor Evolution and Acquired Resistance. In the context of cancer, lineage plasticity is the ability of tumor cells to transition from one developmental pathway to another. Talks in this session will discuss how this lineage plasticity serves as a mechanism of therapeutic resistance. This session will be chaired by Charles Rudin, from the Memorial Sloan Kettering Cancer Center. He will be giving a talk on strategies his group is using to constrain lineage plasticity in prostate cancer. Katerina Politi, from the Yale Cancer Center, present her findings on the resistance to tyrosine kinase inhibitors in lung adenocarcinomas due to lineage plasticity using epigenetic processes. Thomas Graeber, from The Broad Stem Cell Research Center at UCLA, will present data on his lab’s work on the underlining the mechanisms of resistance to BRAF inhibition during treatment of melanoma. To combat this resistance, his lab has been investigating how ferroptosis-inducing drugs can be used to increase the efficacy of targeted and immune therapies.

On Sunday, April 7th there will be a session titled: “Unlocking Spatial Complexity: Harnessing Machine Learning for Spatial Biology Insights.” In this session, recent advances in spatial technologies will be discussed. Talks will cover how spatial transcriptomics have revolutionized our understanding of genes and proteins in tissues, offering detailed analysis at cellular and subcellular levels. These breakthroughs have provided crucial insights from patient samples like tumor biopsies, aiding in treatment selection and understanding treatment responses. To tackle the complexity of spatial datasets, this session focuses on addressing computational challenges in spatial biology and showcases the application of machine learning algorithms to decode tissue structure and cellular organization, particularly in cancer research. During this session Raphael Gottardo of CHUV Lausanne University Hospital in Switzerland will give a talk on the computational challenges faced when using data from spatial biology experiments. His lab recently published a paper in the journal Immunity that describes immune cell interactions within the tumor microenvironment, providing insights into tumor immune evasion mechanisms and potential therapeutic avenues.

On Monday morning, April 8 there will be a session titled Profiling Tumor Ecosystems in Native Tissue Context chaired by Christine A. Iacobuzio-Donahue. Her lab takes the approach that cancer is a disease of evolution and thus is subject to Darwinian selection. The Iacobuzio-Donahue lab utilizes Pancreatic cancer as a model system due to its high metastatic rate and low survival rates. Her research aims to describe how subclonal genetic evolution within primary tumors selects for metastatic phenotypes, and whether specific genetic alterations target core pathways leading to metastasis. They also investigate the morphologic, immunologic, and microenvironmental characteristics of pro-metastatic subclones. The goal of the lab is to find translational and therapeutic opportunities by studying the real-time dynamics of Darwinian selection in human cancer cells across various tumor types. Also in this session, Joakim Lundeberg, from the Science for Life Laboratory in Sweden, will gave a talk on using spatial biology to describe the cancer ecosystem on breast and prostate cancer. His lab studies the build-up of mutations that occur premalignant cells and how certain cells undergo clonal expansion. In his talk he will discuss the molecular interactions between cancer cells and other cell types in the tumor microenvironment (TME). These other cell types the cancer cells interact with are often immune and other tumor-associated cells. To characterizing these TME interactions, his lab uses multiomics computational and experimental methodologies approaches on tumor tissue sections to understand the mechanisms driving malignant transformation. By using high-resolution spatial gene expression data, they are able spatially map B-cells and T-cells (BCR and TCR repertoire) in the MTE and create 3D models of the tumor ecosystem.

Later in the day on Monday April 8th there will be a session focusing on the Understanding and Predicting Tumor Evolution. This session will be chaired by Andrea Sottoriva, the Head of the Computational Biology Research Centre at Human Technopole. He will also give a talk titled ” Darwinian evolution of the epigenome and non-Darwinian cell plasticity in cancer.” His lab is interested in the co-evolution of both genomic and epigenetic changes that cause phenotypic variation between cancer cells.

On Tuesday morning, April 9th there will be a session titled “Evolution of the Genome, Microenvironment, and Host through Metastasis.” In this session, David Lyden, of Weill Cornell Medicine in New York City will discuss multi-organ systemic therapies to combat metastatic disease. His lab is interested in molecular, cellular, and metabolic alterations that cause the formation of pre-metastatic niches (PMNs). These PMNs become future sites of metastasis. His laboratory has been working on finding the differences in PMNs based on the organs, such as the lung, liver, and pancreas, that they originate from. They are using this information to develop therapies for metastatic disease prevention with the knowledge that the treatment must target multiple organs.

Also, during this session, Sarah-Maria Fendt from VIB-KU Leuven in Belgium, will discuss the metastasis mouse models her lab is using to study lung metastases in patients with breast cancer. Specifically, they are investigating the aggressiveness of cancer cells in metastases that is driven by metabolite signaling. They are now using inhibitors that target the molecular mechanism of the metabolite signaling in mouse models to block metastasis formation.

Keywords: Tumor microenvironment (TME), tumor evolution, spatial biology, transcriptomics, genomics, multiomics, single cell analysis, lineage plasticity, prostate cancer, lung cancer, breast cancer, melanoma.

PAG 31 Conference Preview

The 2024 International Plant & Animal Genome Conference (PAG 31)


For over three decades, the Plant and Animal Genome Conference (PAG) has been a meeting known for fostering collaboration, and showcasing groundbreaking advancements in the fields of plant and animal genomics. Established in 1993, PAG has evolved into a conference that converges experts, emerging talents, and innovators in genomics. This year’s PAG 31 is set to take place from January 12-17, 2024, in San Diego, CA, USA.

This year, the conference will include the following plenary speakers: Appolinaire Djikeng (Centre for Tropical Livestock Genetics and Health), Scott Edwards (Harvard University), Lucy van Dorp (University College of London), Katrien M. Devos (University of Georgia), Amy Marshall-Colón (University of Illinois Urbana-Champaign), Dirk Inzé (VIB-UGent Center for Plant Systems Biology), Virginia Walbot (Stanford University). Notable among them is Scott Edwards from Harvard University, who will lead the Plenary Session on “Comparative Population Pangenomes: A New Frontier for the Evolutionary Analysis of Birds.” Edwards’ expertise in evolutionary biology promises an enlightening exploration into avian genomics, unveiling new frontiers in our understanding of bird populations and their evolution.

The Scientific Programs at PAG 31 present diverse workshops, each dedicated to unraveling distinct facets of genomics. From decoding biodiversity to exploring the intricacies of genome annotation, attendees can expect a comprehensive dive into a wide array of workshops. If you are attending this year’s meeting, here is a list of sessions you might not want to miss.

 

Day 1, Jan 12, 2024 (Fri)

Vertebrate Genomes Project: Completing Phase 1: Led by Erich Jarvis, this session will give an overview of Phase 1 of the Vertebrate Genomes Project (VGP). The VGP project aims to generate near error-free reference genome assemblies of ~70,000 extant vertebrate species. The goal for phase 1 is to create a chromosome level assembly for 260 vertebrate orders. A talk by Andreas Pfenning from Carnegie Mellon University will highlight the session. His talk will describe how the genomes from the ordinal lineages sequenced in phase 1 are used to detect signatures of genome sequence evolution. Specifically, he will compare coding and noncoding sequences in the genome and how they evolve.

ORG.one Genomes for Conservation of Critically Endangered Species – ORG.one is a pilot-stage initiative sponsored by Oxford Nanopore designed to expedite the sequencing of critically endangered species. Through this project, biologists are able to rapidly sequence species near the individual’s habitat without harming or sacrificing the endangered individual. This workshop will highlight the latest developments in organizational initiatives, sequencing facilities, and the creation of de novo reference genomes. Discussions will delve into recent progress in nanopore sequencing, genome assembly, annotation, and their practical use in conservation genomics. Aziz Ebrahimi of Purdue University will present his research on the white walnut tree. Gabrielle Hartley of the O’Neil lab at the University of Connecticut will be giving a talk on the Eastern Hoolock Gibbon and the rapid karyotype evolution of small apes.

Animal Genomics and Adaptation to Climate Change: This workshop will provide insight on the implications of climate change for animal agriculture, spanning extreme weather, drought, heatwaves, and shifts in pathogen distribution. These elements significantly impact food security and animal farming across both well-equipped and under-resourced global regions. Understanding the genomic and physiological responses of animals facing climate change is pivotal in devising strategies to counter its adverse effects. This enables the use of tactics like breeding climate-resilient animals and adopting innovative management methodologies. One of the talks will be by Jared Decker from the University of Missouri. The title of his talk is “Matching Cattle Genetics to the Environment Using Genomics.” He will discuss genotype-by-environment genome-wide association analyses his lab has run on cattle in his talk.

Spatially Resolved Transcriptomics in Plant and Animal Species

New developments in spatial transcriptomics have improved the ability to identify cell types, map cell-fate lineages, and unveil interactions between cells. The ability to characterize gene expression across the entire genome at a subcellular level is crucial for defining single-cell functions and understanding their microenvironments. The strengths and weaknesses of technologies will be discussed. An emphasis on the importance of having complete transcriptome data, as opposed to only having a small panel of genes, will be discussed. The importance of having subcellular resolution will also be addressed. During this session, Mathew Lewsey will give a talk titled “Spatially Resolved Transcriptomic Analysis of the Germinating Barley Grain.” His talk will outline the changes in gene expression during early plant development. This is the phase when the embryo undergoes cellular transitions to become a seedling. Later, during the session, Marc Libault from the University of Missouri will present how his lab uses spatially resolved transcriptomics and metabolomics to understand the cellular complexity in plants.

 

Day 2, Jan 13, 2024 (Sat)

Single Cell Genomics: This workshop will cover transcriptomics at the cellular level using single-cell analysis techniques. The analysis will be presented using omics approaches and integrating multi-omics data from single cells using novel computational methods. During this session, Gunvant Patil, from Texas Tech University, will present single nucleus RNAseq (snRNAseq) data and gene-editing results to characterize cellular heterogeneity and transcriptional dynamics in soybean leaf. His presentation will focus on the genes and pathways required for the cell-specific accumulation of minerals (ex. Silicon). Also, during this workshop, Maggs X, from Wes Warren’s lab at the University of Missouri, will deliver a talk on a whole brain transcriptome atlas for the blind cavefish (Astyanax mexicanus). Their transcriptome atlas has been supplemented with snRNAseq data from Pachón cave and Rio Choy surface populations. These two populations differ because the Rio Choy population is exposed to sunlight, whereas the Pachón cave population is cave-dwelling and not exposed to sunlight. The single cell data presented will be from over 60,000 cells with 16 broad cell types. Their project aims to shed light on why cave morphs have dysregulated circadian rhythms, reduced aggression, and differences in sensory processing compared to their surface living relatives.

Scott Edwards will give his plenary talk titled “Comparative Population Pangenomes: A New Frontier for the Evolutionary Analysis of Birds.” His lab is investigating how noncoding regions of the genome are driving phenotypic evolution. He will describe how enhancers regulate gene expression to create diverse phenotypes. To accomplish this, his group is developing statistical models that detect evolutionary changes in enhancer sequences that are associated with phenotypic variation within and between species. To validate these statistical models, his lab plans to functionally test how enhancer variations change the development of the forelimb and hindlimbs in birds.

  

Day 3, Jan 14, 2024 (Sun)

Computational Gene Discovery – This workshop will provide an update on algorithms and software tools (pipelines) for plant and animal genome annotation. Evgenia Kriventseva will discuss the improvements made in ortholog annotation by the new OrthoDB release 11. This latest release provides analysis and annotation for over 100 million genes. Evgenia will also discuss how BUSCO is being used to assess the quality of assembled metagenomes. Also, during this session, Cynthia Webster will introduce EASEL (Efficient, Accurate, Scalable Eukaryotic modeLs). This new genome annotation tool utilizes machine learning, RNA folding, and functional annotations to improve gene prediction accuracy.

Degraded DNA and Paleogenomics – This session will include leading experts in the field of ancient DNA research. In this session, Jonas Oppenheimer will discuss the use of ancient DNA for historical bison populations. Jonas will present evidence from ancient DNA samples to support that bison migrated from Asia across the Bering Land Bridge into the Americas within the past 200,000 years. Once in the Americas, bison separated into two subspecies: wood and plains bison. Later in this session, Beth Shapiro will discuss how genomic data is being used for the hybridization of bison with cattle to create specialized breeds known as cattalo and beefalo. Love Dalen, from Stockholm University, will finish the session with a talk on the biogeography and evolution of North American mammoths. His talk will highlight the gene flow between different mammoth taxa.

 

Day 4, Jan 15, 2024 (Mon)

Genomics & Biodiversity:

Biodiversity genomics is a rapidly emerging field that captures biological diversity from DNA to ecosystems. Genomics advancements will enhance our understanding of Earth’s biodiversity, promising discoveries vital for present and future societies. This session will discuss how next-generation genomic technologies are being used to describe biological diversity patterns and the mechanisms driving diversification. The topics covered will explore links between genetic variance, biodiversity, and a sustainable world’s health, fostering broader engagement in this exploration.

 

Day 5, Jan 16, 2024 (Tue)

Functional Annotations of Animal Genomes (FAANG):

The workshop’s primary objectives include:

1) facilitating the sharing of recent FAANG initiatives globally.

2) creating a dynamic platform for the FAANG community to communicate, fostering interactions and collaborations.

During this workshop, Christopher Tuggle, from Iowa State University, will discuss how to assess the success of FAANG and how this can be used for funding the FAANG Farm to Fork agenda. Emily Clark from The Roslin Institute at the University of Edinburgh will provide an update on The H2020 Bovreg Project: An Integrated Functional Annotation of the Bovine Genome. In this talk, she will describe how a diverse dataset, including ChIPseq, ATACseq, RRBS, and WGMS data, was used for the functional annotation of the Bovine Genome. David Hawkins, from the University of Washington, will be giving a similar presentation, but on the functional annotation of the chicken genome.

Bioinformatics: This workshop will focus on the computational tools used for the interpretation of biological data and understanding genomics. This workshop is being led by Aleksey Zimin. During this workshop, Alexandre Lomsadze, from Georgia Tech, will describe the improvements in performance and accuracy of GeneMark-ETP over GeneMark-ET or GeneMark-EP+ for gene predictions. In addition, Haoyu Cheng, from Harvard Medical School, will characterize the HiFiasm assembler. HiFiasm requires PacBio HiFi, ONT ultra-long, Hi-C reads, and trio data. Haoyu will present the results of HiFiasm assemblies from 22 human and two plant genome assemblies.

Galaxy for NGS Data Analysis: This session will be a hands-on workshop that will first introduce the Galaxy platform. The session will also include a hands-on tutorial on the QC, classification, and analysis of metagenomes using short and long-read sequencing data.

 

Day 6, Jan 17, 2024 (Wed)

Wildlife Genomics: This workshop will discuss the evolutionary and population genomics of wild animals. Aryn Wilder, from the local San Diego Zoo, will present an update on the zoo’s conservation efforts on the Northern White Rhino. Using the southern white rhinos as a benchmark, they are running simulations on the viable fitness of restoring the Northern White Rhino using biobanked cells. Also, during this session, Mikkel-Holger Sinding, from the University of Copenhagen, will be giving a talk on three Asian Bos lineages: gaur (Bos gaurus), banteng (Bos javanicus), and the extinct kouprey (Bos sauveli). Using genomic data from historical samples, his group found that banteng is a paraphyletic group with several Bos species lineages. He suggests that these lineages are a result of significant admixture events.

 

 

Keywords: Bioinformatics, Population Genomics, Conservation Genomics, Spatial Biology, Single Cell Genomics, Spatial transcriptomics, Multi-omics, Paleogenomics, Ancient DNA, Agrigenomics, Computational Biology.

Reflecting on the AACR General Conference 2023, Orlando, Florida

To start the 2023 AACR meeting, AACR CEO Margaret Foti welcomed everyone and gave opening remarks. She said as the number of cancers around the world are increasing, it is leading to the pursuit of transformative research. She emphasized the need for collaborative studies between cancer center institutes across the US. She then announced the 312 new research fellows for the AACR academy. She also mentioned that members of AACR need to develop strategies to include underrepresented minorities in cancer clinical trials. As an example, she discussed a grant from Bristol Myers Squib which main aim is to develop strategies on how to recruit and include underrepresented groups in cancer clinical trials.

Margaret Foti’s talk was followed by talk from the current AACR president, Lisa M. Coussens, from the OHSU Knight Cancer Institute. She first thanked AACR staff for their support during her role as the AACR president. During her talk, emphasized the importance of basic research. She mentioned that there is not an instance where there is a therapeutic on the market whose development was not built on a basic science discovery. She said basic science led to biomarkers for early detection and response to treatment, new mechanisms, new therapeutic targets. She then discussed the importance of bringing translational science to the patient. As an example, she discussed the AACR project GENIE (Genomics Evidence Neoplasia Information Exchange) initiative for precision medicine. One of the goals of the GENIE project is to facilitate clinicogenomic data sharing with international cancer centers and pharmaceutical companies. She highlighted that as of this past January, this initiative led to over 167,000 samples sequenced from over 148,000 patients. This information has been made publicly available. As a part of the GENIE project, she announced 4 new cancer centers (Children’s Hospital Los Angeles, Korea University Anam Hospital, LSU Health New Orleans, and the Sylvester Comprehensive Cancer Center). These new centers were chosen based on their ability to genomically profile and treat diverse and underrepresented patient populations. Lisa Coussens concluded her talk by stating that the AACR endorses President Bidens cancer moonshot program. The Cancer Moonshot program aims to reduce cancer mortality by 50% over the next 25 years through cancer prevention and early detection along with developing new approaches to treat rare and deadly cancer types. Including pediatric cancers. She then closed by welcoming Phillip Greenberg as the next AACR president.

After Lisa Coussens’ talk, Pamela Ohashi announced the 2023 AACR lifetime achievement award to Dr. Karl H Jun, from the University of Pennsylvania, for his work in cancer immunotherapy. His lab was the first to introduce gene edited therapy for cancer.

During the AACR conference there were several major symposiums that shed light on the newest technologies that are being used for translation research. One session that stood out was the symposium on Spatial Technologies for Mapping Cancer Cell Architecture. This session was highlighted by talks from Alexander Swarbrick, from the Garvan Institute of Medical Research in Australia, and Itai Yanai, from the Grossman School of Medicine at NYU.

Alexander Swarbrick’s talk was titled spatial mapping of breast cancer cellular ecosystems. His lab approaches tumors as a dynamic ecosystem consisting of three levels.

  1. Taxonomy (single cell) – different cells that comprise a tumor.
  2. Spatial – where the cells are within the tumor space.
  3. Phenotypic – be able to determine the phenotype in the patient and understand how that can be used to diagnostics and treatment.

His lab used this ecosystem approach to create a breast cancer atlas a result of multiple stages of cancers collected over several years.

During his talk, he described a method his lab uses called SPITE-Seq (Spatial Cellular Indexing of Transcriptomes & Epitopes). SPITE-Seq is based on CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes) which was developed out of the NY Genome Center. Initially, he used ~150 barcoded antibodies to combine with transcriptome data for spatial resolution. However, the data from 150 antibodies was not easily managed, so they thinned down the list of proteins to target using several methods developed in house.

Ultimately, his lab wanted to investigate if the regions within a tumor with different transcriptional profiling represented different genomic clones. To investigate this, they used Cytasssist on archival FFPE samples to look at regions with unique copy number variations (CNV) in the genome using the infer-CNV tool. Infer-CNV uses sliding windows across the genomes representing 100 genes per segment to detect coordinated changes in gene expression. This enabled their lab to infer copy number gains and loses across the genome which could be spatially resolved in an invasive carcinoma.

His lab recently began a collaboration with Joakim Lundaberg’s group from SciLifeLab in Sweden. Together they are going to expand their analysis on over 250 diverse breast cancer samples containing both scRNA-seq data and spatial transcriptomic data.

The next talk, by Itai Yanai, was titled Mapping cellular plasticity in tumor progression and drug resistance. He showed data demonstrating that cancer cells are transcriptionally heterogeneous. His work focused on identifying regions of the tumor with gene enrichments. To do this, he studied 62 tumors of different cancer types. He Identified gene modules in each tumor using scRNA-seq. Each of these modules contained enrichments of 20-200 genes. Typically, each tumor contained several modules, of which he looked for dominant modules. He analyzed these dominant modules across tumor types.

Later in his talk, he stepped back and discussed how he views the creative side of the scientific process. He likes to divide his approach to science into two parts: day science and night science. He considers day science to be primarily for hypothesis testing and night science to be where he generates his hypotheses. He then mentioned his podcast, Night Science, that goes into detail on this. In his podcast with Martin Lercher, he invites a guest scientist to explore the creative side of science. This led him to a discussion on spatial transcriptomics and how it can be used as on opportunity for identifying nano-environments in diverse cancer types. With that in mind, he did caution that low resolution plafforms, such as Visium, are not suited for hypothesis testing. However, they are good for hypothesis generation. This is because for Visium, each spot contains 5-10 cells. This means you need to infer which spots only have malignant cells. However, since there are multiple cells per spot, each spot may have both malignant and non-malignant cells.

On Thursday, April 20th AACR 2023 closed out with a recap symposium titled 2023 Highlights: Vision of the Future. The first talk was by Robert Vonderheide, the Director of the Abramson Cancer Center at the University of Pennsylvania. During his talk, he mentioned that he was impressed on the number of presentations and posters on pre-malignancy. He said that although it is important to understand invasive cancers, it is critical to understand cancers in their earliest stages. He believes that our biggest impact on the fight against cancer will be a result of our deep understanding of these early stages of cancer. He mentioned that some incredible strong, laboratory driven science that has been presented at this meeting. He made a special note on how much details about the LAG3 cell surface protein have been worked out and the sustained power of immuno-oncology. He was also pleased to see the progress that has been made with community outreach and engagement, health equity, data science, artificial intelligence, new technologies. He also made note of the incredible presence of strong clinical science at the meeting. This year there was a record number of submitted abstracts on the results of clinical trials.

One of the following speakers was Elizabeth Platz from the Johns Hopkins Bloomberg School of Public Health. Her talk title was Prevention, early detection, population sciences and disparities research. To begin her talk, she discussed a recently published paper in the journal Cancer Discovery by Meredith Shields. The title of the Shields et al. paper is “Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047.” The main theme of the paper was that action is going to be needed to be able to achieve the moonshot goal. The action she suggested was based on behavioral economics and nudges to improve cancer care and increase screening. She mentions systems, protocols, and information that can be put in place to motivate individuals and patients and providers to taking action. Elizabeth also mentioned Kelsey Lau-Min presentation that encouraged decision making to be guided more efficiently. For example, when ordering a test, make it automated as an opt out rather than an opt in. She also mentioned optimizing precision oncology care through nudges. She brought up examples of reflex biomarker testing, interpretation, and treatment matching all along the continuum to patient precision testing. The caveat of these strategies is that they do involve lots of subspecialty expertise. So, for these to work, the workflow has to be optimized. There needs to be a bioinformatics pipeline and it must all be embedded within the electronic medical system. Towards the end of Dr. Platz’s talk, she discussed a group’s research addressing African genetic ancestry and trying to understand whether that ancestry can explain higher risks of certain cancers like head and neck cancers. She noted that it was previously showed that US and global populations with African ancestry have notable genetic diversity. She then discussed work that suggested genetic diversity can affect treatment response, especially when DNA repair genes are involved.