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The American Association for Cancer Research’s (AACR) annual meeting is one of the largest gatherings of scientists and clinicians to share their progress in combating the world’s leading cause of death. This year’s event took place at the Orange County Convention Center in Orlando, Florida. The meeting was filled with extraordinary research and important discussions about the latest developments in cancer research and treatments. Below are some of the highlights of AACR 2023 handpicked by our editorial team.
Important Talks and Research
Cancer Moonshot
An important discussion took place between the National Cancer Institute’s (NCI) Director, Dr. Monica Bertagnolli, and AACR President, Dr. Lisa M. Coussens. The officials spoke about the White House’s Cancer Moonshot goal of reducing cancer mortality by 50% over the next 25 years and how the NCI plans to accomplish the task. The current NCI strategy involves eight essential goals and associated strategies that detail what must be done to keep pace with these targets. One important theme during the discussion was the issue of funding. While Bertagnolli mentioned that the NCI budget has increased, the year-on-year investment must continue in order to advance cancer research. Along with the official commentary, an NCI paper written on the subject was published in the AACR journal Cancer Discovery.
Cancer Vaccine
Oncologists Jeffrey S. Weber, MD, Ph.D. and Ryan Sullivan, MD, participated in a media briefing where they reported the results from a phase 2 clinical trial (KEYNOTE-942) that involved a combination of pembrolizumab and a personalized mRNA-based cancer vaccine. The selected patients had high-risk melanoma and those receiving both treatments showed a 44 percent reduction in the risk of recurrence or death compared to patients receiving pembrolizumab alone after two years of follow-up. The vaccine, mRNA-4157, is a customizable therapy that encodes up to 34 neoantigens derived from the patient’s own tumor. It was the first successful cancer vaccine trial in melanoma. The clinicians reported that a longer follow-up will be needed and that a phase III trial is set for this summer.
Targeting KRAS
A plenary session focused on the progress of targeting KRAS for cancer therapies. Once thought to be undruggable, sotorasib (Lumakras) and adagrasib (Krazati) are two drugs used today to target KRAS, while other therapies like the investigational KRAS inhibitor BBO-8520 are currently being evaluated. Researchers discussed these topics along with the possibilities of combining treatments to improve outcomes. Read more from the AACR website.
Single-cell Research Investigates Brain Tumor Metastases
A new study involving scientists from the University of Texas MD Anderson Cancer Center resulted in the creation of the largest single-cell atlas of brain metastases from renal cell carcinoma (RCC) with matched primary and extracranial metastases. RCC is the most common type of kidney cancer and is particularly problematic to treat once it metastasizes to the brain. After obtaining better insights into the tumor’s microenvironment, the researchers plan to pursue further preclinical and clinical trials to test various combination therapies and identified targets in combination with immune checkpoint inhibitors for patients with RCC brain metastases.
Colorectal Cancer Patients with African Ancestry
Genomic profiling of colorectal cancer patients at Memorial Sloan Kettering Cancer Center (MSK) between 2014 and 2022 found that patients of African ancestry had fewer actionable mutations than patients of European ancestry, and were less likely to qualify for treatment with immunotherapy. Patients of African ancestry had lower rates of clinically actionable alterations than patients of European ancestry, which may mean that they have fewer options for targeted therapies and immunotherapies that could improve outcomes for many colorectal cancer patients. The study's findings suggest that somatic alterations could play a role in the persistent racial disparities in colorectal cancer and that additional studies are critical for improving clinical outcomes.
Exciting Posters
Sequencing a new broadly-consented tumor/normal cell line for a Genome in a Bottle Benchmark
Gail Rosen et al. described their analyses with new cell lines from a broadly-consented pancreatic ductal adenocarcinoma patient for the first tumor/normal benchmark from the Genome in a Bottle (GIAB) consortium. In their analysis, they describe many different types of variants within the cells. Future plans for the GIAB are to perform PacBio’s HiFi and ONT’s ultra-long sequencing to generate phased assemblies for both the normal and tumor cells. Additionally, they plan to form an open working group to develop the first authoritative benchmarks from publicly available, broadly-consented tumor-normal cell lines.
Phylogenetic reconstruction across 303 metastatic tumor samples using Ultima whole-genome sequencing dramatically increases subclonal resolution
Julian Hess et al. performed deep whole genome sequencing using the UG100 sequencer (Ultima Genomics) to demonstrate a comprehensive characterization of tumor evolution. After identifying 32 patients with various cancer types, they collected multiple samples per patient and sequenced them to an average coverage of 63x. They then constructed phylogenetic trees which were much more detailed and consistent with previous work than data generated from whole exome sequencing (WES). The authors believe that whole genome sequencing projects like this, “will be performed at ~1/6th the cost of current NGS offerings (on par with current WES costs).”
Genomic landscape of prostate cancer: Bioinformatic analysis of TCGA PanCancer data by race and identification of key pathways and genes in PTEN mutation
Olumide Arigbede et al. examined PTEN (Phosphatase and Tensin Homolog), the most often mutated gene in Prostate cancer (PCa). The researchers used The Cancer Genome Atlas (TCGA) to study PCa gene expression and DNA methylation data by race/ethnicity, gene expression, DNA methylation, and genomic changes. They found significant differences by race/ethnicity in every category of data assessed. PTEN mutation was found in 20% of patients, and several genes, including SLC2A1, NUDT12, and CUTALP, were associated with survival.
Mathematical modeling of single-cell data reveals the key role of stochasticity - not fitness - in determining the clonal origins of relapse in childhood leukemia
Virginia Turati et al. investigated childhood, acute lymphoblastic leukemia (cALL) to better understand the relapse genetic landscape. They used single-cell WGS and RNA-seq data from primary and xenografted leukemic cells before and after chemotherapy. The resulting data was used to parameterize an agent-based mathematical model, which allowed them to follow the genotype and evolving phenotype of individual cells over time. Their results showed that, “the size of residual disease and a founder effect linked to the stochastic exit, post-treatment, of individual cells from quiescence were the key determinants of the relapse genetic landscape.”
Common Trends
Closing Thoughts
There’s so much more our team wishes we could include in this wrap-up. These highlights barely scratch the surface of all the incredible research presented at the meeting. So instead of adding more to this article, we’ll instead ask the community.
What were some of your highlights and favorite parts of AACR? Make sure you're logged in, so you can share your thoughts in the comment section below! Once you log in you'll see the comment box.
Important Talks and Research
Cancer Moonshot
An important discussion took place between the National Cancer Institute’s (NCI) Director, Dr. Monica Bertagnolli, and AACR President, Dr. Lisa M. Coussens. The officials spoke about the White House’s Cancer Moonshot goal of reducing cancer mortality by 50% over the next 25 years and how the NCI plans to accomplish the task. The current NCI strategy involves eight essential goals and associated strategies that detail what must be done to keep pace with these targets. One important theme during the discussion was the issue of funding. While Bertagnolli mentioned that the NCI budget has increased, the year-on-year investment must continue in order to advance cancer research. Along with the official commentary, an NCI paper written on the subject was published in the AACR journal Cancer Discovery.
Cancer Vaccine
Oncologists Jeffrey S. Weber, MD, Ph.D. and Ryan Sullivan, MD, participated in a media briefing where they reported the results from a phase 2 clinical trial (KEYNOTE-942) that involved a combination of pembrolizumab and a personalized mRNA-based cancer vaccine. The selected patients had high-risk melanoma and those receiving both treatments showed a 44 percent reduction in the risk of recurrence or death compared to patients receiving pembrolizumab alone after two years of follow-up. The vaccine, mRNA-4157, is a customizable therapy that encodes up to 34 neoantigens derived from the patient’s own tumor. It was the first successful cancer vaccine trial in melanoma. The clinicians reported that a longer follow-up will be needed and that a phase III trial is set for this summer.
Targeting KRAS
A plenary session focused on the progress of targeting KRAS for cancer therapies. Once thought to be undruggable, sotorasib (Lumakras) and adagrasib (Krazati) are two drugs used today to target KRAS, while other therapies like the investigational KRAS inhibitor BBO-8520 are currently being evaluated. Researchers discussed these topics along with the possibilities of combining treatments to improve outcomes. Read more from the AACR website.
Single-cell Research Investigates Brain Tumor Metastases
A new study involving scientists from the University of Texas MD Anderson Cancer Center resulted in the creation of the largest single-cell atlas of brain metastases from renal cell carcinoma (RCC) with matched primary and extracranial metastases. RCC is the most common type of kidney cancer and is particularly problematic to treat once it metastasizes to the brain. After obtaining better insights into the tumor’s microenvironment, the researchers plan to pursue further preclinical and clinical trials to test various combination therapies and identified targets in combination with immune checkpoint inhibitors for patients with RCC brain metastases.
Colorectal Cancer Patients with African Ancestry
Genomic profiling of colorectal cancer patients at Memorial Sloan Kettering Cancer Center (MSK) between 2014 and 2022 found that patients of African ancestry had fewer actionable mutations than patients of European ancestry, and were less likely to qualify for treatment with immunotherapy. Patients of African ancestry had lower rates of clinically actionable alterations than patients of European ancestry, which may mean that they have fewer options for targeted therapies and immunotherapies that could improve outcomes for many colorectal cancer patients. The study's findings suggest that somatic alterations could play a role in the persistent racial disparities in colorectal cancer and that additional studies are critical for improving clinical outcomes.
Exciting Posters
Sequencing a new broadly-consented tumor/normal cell line for a Genome in a Bottle Benchmark
Gail Rosen et al. described their analyses with new cell lines from a broadly-consented pancreatic ductal adenocarcinoma patient for the first tumor/normal benchmark from the Genome in a Bottle (GIAB) consortium. In their analysis, they describe many different types of variants within the cells. Future plans for the GIAB are to perform PacBio’s HiFi and ONT’s ultra-long sequencing to generate phased assemblies for both the normal and tumor cells. Additionally, they plan to form an open working group to develop the first authoritative benchmarks from publicly available, broadly-consented tumor-normal cell lines.
Phylogenetic reconstruction across 303 metastatic tumor samples using Ultima whole-genome sequencing dramatically increases subclonal resolution
Julian Hess et al. performed deep whole genome sequencing using the UG100 sequencer (Ultima Genomics) to demonstrate a comprehensive characterization of tumor evolution. After identifying 32 patients with various cancer types, they collected multiple samples per patient and sequenced them to an average coverage of 63x. They then constructed phylogenetic trees which were much more detailed and consistent with previous work than data generated from whole exome sequencing (WES). The authors believe that whole genome sequencing projects like this, “will be performed at ~1/6th the cost of current NGS offerings (on par with current WES costs).”
Genomic landscape of prostate cancer: Bioinformatic analysis of TCGA PanCancer data by race and identification of key pathways and genes in PTEN mutation
Olumide Arigbede et al. examined PTEN (Phosphatase and Tensin Homolog), the most often mutated gene in Prostate cancer (PCa). The researchers used The Cancer Genome Atlas (TCGA) to study PCa gene expression and DNA methylation data by race/ethnicity, gene expression, DNA methylation, and genomic changes. They found significant differences by race/ethnicity in every category of data assessed. PTEN mutation was found in 20% of patients, and several genes, including SLC2A1, NUDT12, and CUTALP, were associated with survival.
Mathematical modeling of single-cell data reveals the key role of stochasticity - not fitness - in determining the clonal origins of relapse in childhood leukemia
Virginia Turati et al. investigated childhood, acute lymphoblastic leukemia (cALL) to better understand the relapse genetic landscape. They used single-cell WGS and RNA-seq data from primary and xenografted leukemic cells before and after chemotherapy. The resulting data was used to parameterize an agent-based mathematical model, which allowed them to follow the genotype and evolving phenotype of individual cells over time. Their results showed that, “the size of residual disease and a founder effect linked to the stochastic exit, post-treatment, of individual cells from quiescence were the key determinants of the relapse genetic landscape.”
Common Trends
- Members we spoke with during the meeting shared their enthusiasm that the meeting had a focus on translation research and wasn’t overwhelmed with pharmaceutical and clinical announcements.
- The organizers of the AACR annual meeting have made it clear that the event won’t become repetitious, with each year focusing on different, influential scientists. Their efforts were apparent in this year’s presentations which highlighted many promising young scientists making a big impact on cancer research.
- AACR leadership is putting an emphasis on finding better ways to validate and utilize new technologies. They acknowledged the difficulty of this process, but are determined to find better ways for their implementation. In addition, they will also assist the research community to find solutions for storing, standardizing, and accessing data accumulated from their research.
Closing Thoughts
There’s so much more our team wishes we could include in this wrap-up. These highlights barely scratch the surface of all the incredible research presented at the meeting. So instead of adding more to this article, we’ll instead ask the community.
What were some of your highlights and favorite parts of AACR? Make sure you're logged in, so you can share your thoughts in the comment section below! Once you log in you'll see the comment box.