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.