Highlights from AACR2022

Apr 29, 2022

By Dorys LopezAfter two consecutive years of virtually holding the annual meeting of the American Association for Cancer Research (AACR), the conference returned to an in-person format, while retaining a hybrid option for those who prefer to join virtually. There were over 19,000 registrants, with approximately 78% attending in-person, according to Margaret Foti, chief executive officer of the AACR.

One of our team members is a seasoned AACR attendee, with this being her 24th AACR annual meeting. For the rest of us newbies, we could not have imagined the extent of the conference: from the breath of topics covered by countless posters, talks and booths, to the size of the convention center. There was so much to take in with a three-day period (without counting the educational program). It was encouraging to see all the exciting research emerging in the cancer field and even more exciting to be part of it. Our team did a great job presenting nine posters, all highly attended, addressing high impact questions in cancer care across a spectrum of topics.

It would be impossible to cover the entire variety of topics presented at the conference, so we selected a couple of them to highlight:

Cancer disparities. This topic was discussed throughout many sessions. During a plenary session, Mariana Stern, Director for the Molecular Epidemiology MS/PhD Program at USC, emphasized the importance of progress in cancer research reaching all populations and individuals. Cancer research has mainly relied on samples that come from Caucasian (white) patients. Efforts are now in place to increase diversity, to understand how race and ethnicity influence patient care and outcomes. Melissa Davis, Scientific Director of the International Center Study of Breast Cancer Subtypes, talked about the impact of genetic ancestry and social determinants on disparities, focusing primarily on African ancestry and how it relates or differs from observations in African American cohorts. A full session was dedicated to breast cancer genomics in Latin America, where Laura Fejerman, Associated Professor in the Department of Public Health Sciences School of Medicine at the University of California Davis, emphasized the lack of diversity in the breast cancer genome-wide association studies (GWAS). She now leads the Latin America Genetics and Genomics of Breast Cancer Consortium (LAGENO-BC), which intends to expand the study of the genetics of breast cancer in Latina women.
Our team presented our latest research on racial can abstract and poster titled “Integrating imaging and multi-omics data to elucidate racial differences in breast tumor biology to optimize precision oncology approaches and patient outcome” where African American tumors in the analyzed cohort grew faster, had more adipose tissue around the tumor, were stiffer and more heterogenous in drug distribution with lower spatial blood flow distribution than tumors from Caucasian patients. We agree that the characterization of racial-specific biological factors is crucial as it may lead to new strategies for personalized treatment.

Triple Negative Breast Cancer (TNBC). A full session was dedicated to this breast cancer subtype. Edison Liu, professor and President Emeritus of The Jackson Laboratory (JAX), identified differences in TNBC response to platinum therapy based on BRCA1 promoter methylation or BRCA1/2 mutations. He found TNBC with BRCA1 promoter methylation to be associated to resistance to platinum therapy, while that is not the case for TNBC with BRCA1 mutations. In line with therapy resistance, Lisa Carey, L. Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research in the Department of Medicine at the University of North Carolina (UNC), talked about the challenges of TNBC therapy. She walked the audience through the therapies that showed preclinical and early clinical promise but failed to reach late clinical phase success, such as therapies targeting EGFR, the PI3K/AKT pathway and the Ras/Raf/MEK pathway. She mentioned the TNBC luminal-androgen receptor (LAR) subtype, and the potential to target this with endocrine therapy, although, until now the clinical rate benefit has been modest (19-20%). A new wave of antibody drug conjugates (ADCs) to treat TNBC is developing. These antibody-drug conjugates target Trop2, a protein expressed on the cell surface of about 80% of TNBCs, although it is also expressed in many healthy cell types. Scituzumab govitecan-hzyi (AB SN38) and Dato-DXd, are two of the ADCs that are being evaluated. Finally, she highlighted the need of better biomarkers for immunotherapy, where PD-L1 works as a biomarker in metastatic TNBC but not in non-metastatic TNBC.
This breast cancer subtype is considered the most aggressive type. Tumor aggressiveness plays an important role in escalation of care for TNBC patients. Our team presented an abstract and poster on “Accurate prediction of tumor growth and doubling times for triple negative breast cancer (TNBC) allows for patient-specific assessment of tumor aggressiveness”. Using TumorScope’s biophysical simulation platform, our team accurately calculated tumor growth (specific growth rate) using RNA-seq data, and tumor volume doubling time (TVDT) using metabolic models. This model can be used to assess the aggressiveness of the tumor in TNBC patients, providing valuable information that could potentially support treatment selection.

Single cell, spatial transcriptomics and spatial analysis of tumors. In the last couple of years, the spatial analysis of tumors has rapidly grown and become a main topic of interest. Research has shown that is not only important to know what type of cells are present in the tumor, it is equally important to understand how they are distributed across the tumor, as well as how they interact with each other and with the microenvironment.
A full minisymposium session and poster section were dedicated to single cell and spatial transcriptomics. Linghua Wang, tenure-track Assistant Professor at Department of Genomic Medicine, explained the many applications of single-cell RNA sequencing approaches during the introduction of the session. With single-cell RNA sequencing it is possible to assess the tumor cell heterogeneity by profiling diverse subpopulation of tumor cell types, cell states, cell composition and tissue distribution. Additionally, it can be used for correlative analysis of biomarkers. With spatial transcriptomics it is possible to do spatial clustering to study cell patterns and cell type decomposition. High-quality data can be extracted from FFPE tissue and integrated with histology to do spatial analysis of these samples. In the Deep Learning in imaging session, Jeremy Goecks, section Head for Cancer Data Science and an Associate Professor of Biomedical Engineering at Oregon Health & Science University (OHSU), talked precisely about deep learning in the context of multiplex tissue imaging as a next generation IHC. He highlighted the use of spatial proteomics assay in FFPE slides, which yield high-dimensional single-cell proteomics data, and spatial position of cells. The applications of this technique for precision oncology include understanding how these features/phenotypes correlate with therapy response, resistance and recurrence. In the same session, Joel Saltz, Cherith Professor and Founding Chair, Department of Biomedical Informatics at Stony Brook University, talked about the use of whole slide imaging to understand tumor lymphocyte infiltration (TILs). He highlighted the use of ‘pathomics’ tissue analytics for precision medicine, specifically to understand the spatial distribution of TILs and how spatial TIL patterns can be used to predict treatment response and outcome, and to stratify patients. Maryam Pourmaleki, a PhD candidate at the Tri-Institutional PhD Program in Computational Biology and Medicine at Weill Cornell Medical College, also talked about the importance of the spatial view of immune cell function in cancer to identify biomarkers of immunotherapy response. In her talk she described different spatial features, such as the presence of MHCI and a certain type of CD8 T cells (PD1+LAG3+TIM3+) in the tumor region of responders to intralesional IL-2 treatment of melanoma. She underscored the spatial topology of the tumor microenvironment as a key to understanding the interplay of the tumor and immune cells.
Our TumorScope technology is able to do spatio-temporal modeling of the tumor microenvironment, whereby modelling nutrient transport and drug behavior it can predict how different regions of the tumor will respond to therapy and how the tumor changes in size, shape and morphology over time. TumorScope’s model was presented in the abstract and poster “Spatio-temporal modeling of the tumor microenvironment for prediction of patient-specific response to chemotherapy”. We are also able to integrate RNA-seq data in a systems biology approach that allows for the identification of different metabolic subtypes that could have therapeutic implications. Our team presented three posters on this topic. An explanation to our systems-based approach can be found in the abstract and poster “Using systems medicine for comprehensive metabolic profiling of tumors: how tumor metabolism shapes prognosis and response to chemotherapy.”

Computational Oncology and artificial intelligence. Computational oncology has been widely used to develop predictive models for drug response. Erica Silva, an MD/PhD candidate at the University of California, talked about Nested Systems in Tumors (NeST) in combination with visible neural networks (VNN), which allow for an understanding of how and why models make their predictions on patients and clinical samples. She built a model for Palbociblib, a CDK4/6 inhibitor used to treat advanced breast cancer. In her study using the project GENIE cohort she showed that her model was specific for Palbociclib response rather than just prognostic of overall survival. Our team also presented data on our predictive model for drug response that is integrated in our TumorScope platform. This data was presented in collaboration with the University of Cincinnati. In the study, TumorScope predicted the response to neoadjuvant therapy (pathological complete response and residual disease) across all breast cancer subtypes with high accuracy (91.2%) in 81 patients. This model accounts for the different types of standard-of-care regimens that the patients received as neoadjuvant therapy, so the predictions are made on a patient-specific manner based on individual patient characteristics from data collected at diagnosis. This data was presented in the abstract and poster “SimBioSys® TumorScopeTM accurately models and predicts response to neoadjuvant therapy in Breast Cancer – Validation study.”

To read the full SimBioSys’ abstracts that were presented at the AACR22 you can click here.

 

TumorScope™ Breast

SimBioSys TumorScope™ currently aids the identification of the safest and most efficacious drug regimens for breast cancer patients.

It provides quantitative and qualitative analysis of a patient’s potential response to therapy, generated with a 3D computational model incorporating previously acquired diagnostic data.

The results from TumorScope™ are intended to be used in conjunction with the oncologist’s professional judgment, patient’s clinical history, symptoms, and other diagnostic tests.

With hundreds of retrospective patients validated, our results speak for themselves – a 95% correlation between simulated final volume and actual clinical volume post-therapy.

The Future
TumorScope™ Brain

Please Stay Tuned

The Future
TumorScope™ Mouth/Throat

Please Stay Tuned

TumorScope™ Lung

SimBioSys is developing TumorScope™ Lung, with the goal of having a positive impact on quality of life, clinical decision-making, and healthcare costs associated with lung cancer.


Though lung cancer is the leading cause of cancer-related deaths worldwide, it is amongst the few solid tumors for which immunotherapeutics have shown great promise.


The structure of lung tissue is dissimilar to that of other tissues we have studied, as the lungs are highly vascularized, oxygenated, and composed of numerous branching sets of airways.


These factors facilitate the need for accurate 3D models of the lung tumor microenvironment, and require nuanced optimization of our image analysis and segmentation methods.

The Future
TumorScope™ Bladder

Accounting for approximately 81,000 new cases in the US each year, bladder cancer is the sixth most-frequently diagnosed solid tumor.

The primary goal of neoadjuvant chemo for advanced bladder cancer is not to enable bladder-conserving treatment, but to downstage the tumor before radical cystectomy.

Bladder cancer staging is strongly dependent on the cancer’s invasion into the bladder wall and surrounding perivesical tissue.

Because of this, the SimBioSys TumorScope™ is poised to offer healthcare providers new methods to predict the degree of downstaging under different treatment regimens, and thereby optimize therapy for patients.

The Future
TumorScope™ Prostate

Affecting approximately 165,000 men in the United States each year, prostate cancers tend to occur in older men, and are often slow to progress.

As a result, management of the disease frequently includes watchful waiting and active surveillance.

SimBioSys TumorScope™ is capable of predicting tumor growth and progression, both with and without intervention.

There exists an obvious application in weighing the risks and benefits of less aggressive approaches to prostate cancer management.

The Future
TumorScope™ Ovary

The “silent killer”, early stage ovarian cancer often presents with symptoms similar to those of other common gynecological or gastroenterological issues.

Approximately 70% of epithelial ovarian cancers are not diagnosed until stage III or IV.

Ovarian cancer represents a natural next step for SimBioSys, allowing us to leverage the knowledge and modeling expertise we’ve accumulated.

This will allow us to target a cancer with high morbidity and mortality, for which neoadjuvant therapy is becoming an increasingly important option.

The Future
TumorScope™ Colon

Please Stay Tuned

The Future
TumorScope™ Skin

Please Stay Tuned

The Future
TumorScope™ Kidney

Please Stay Tuned

The Future
TumorScope™ Liver

Please Stay Tuned

The Future
TumorScope™ Uterus

Please Stay Tuned

The Future
TumorScope™ Thyroid

Please Stay Tuned

The Future
TumorScope™ Pancreas

Please Stay Tuned

The Future
TumorScope™ Esophagus

Please Stay Tuned

Tumor Microenvironment
Modeling

The tumor microenvironment is understood as a complex space where cancer cells adapt their metabolic behavior, competing and cooperating with nearby healthy cells in order to grow.

Understanding the complex ways in which cancer cells interact with other nearby cell types—competing for some resources, sharing others, and eliciting molecular signals that reshape their surroundings—is critical for understanding tumor progression and response to therapy.

SimBioSys TumorScope™ offers a computational window to these interactions, enabling patients and healthcare providers to explore how different treatment regimens can influence tumor response, and ultimately, patient survival.

Virtual Trials

The logistical and financial requirements of clinical drug trials are burdensome in the context of developing novel cancer therapeutics.

Additionally, there is inherent risk for the participants of these trials, both human and animal.

Building on the aforementioned technology, SimBioSys plans to create software to virtually test the efficacy of a drug on our library of patients.

The goal is to use this technology for planning and selecting the most appropriate cohorts, using computational methods, before a trial begins.

Additionally, this technology will be used for testing the effects of various forms of a drug on virtual patients, as opposed to humans or animals.

This technology will provide a deeper understanding of the mechanisms underlying treatment non-response, and will aid in drug development efforts.

Drug Delivery Modeling

After the SimBioSys platform has been extended to nearly the full range of solid mass tumors, pharmaceutical companies will be able to test their numerous therapies against a range of simulated tumors to discover new uses and delivery methods for drugs.

Studies show a salient relationship between sub-optimal drug delivery and acquired drug-resistance, leading to increased risk of mortality.

TumorScope™ provides an opportunity to reduce the likelihood of this occurrence.

Tushar Pandey
Chief Executive Officer MBA University of Chicago, BS Engineering University of Illinois at Urbana-Champaign

With a passion to support the fight against cancer, Tushar’s focus is to ensure the company delivers on its mission to empower precision medicine. In his prior role as VP of Decision Support at Strata Decision Technology, he worked
with over 150 health systems across the country including Kaiser Permanente, Cleveland Clinic, MD Anderson, Intermountain Healthcare, Dana Farber among others. Under his leadership, Strata Decision received the prestigious “Best in
KLAS” recognition for five consecutive years. With over a decade of healthcare experience, Tushar has been one of the key thought leaders in the healthcare analytics and cost of care space.

Joseph R. Peterson
Chief Technical Officer PhD Chemistry University of Illinois at Urbana-Champaign

Driven by an interest in computing, Joseph’s 10 years of scientific research has spanned investigating combustion and explosion, to analyzing the role of the environment on microbes’ behavior, to examining individual differences in
breast tumors. He is passionate about developing software for the health and scientific R&D sectors. His goal as Chief Technical Officer at SimBioSys, Inc. is not merely to develop enterprise technologies that enable new
clinical action, but to foster lasting relationships between key players in cancer treatment.

John A. Cole, Jr.
Chief Scientific Officer PhD Physics University of Illinois at Urbana-Champaign

John is a biophysicist specializing in stochastic models and systems biology. Equally comfortable with pencil-and-paper mathematical modeling and high-performance computational simulation, John’s “whatever works” approach to problem
solving and friendly, collaborative demeanor has allowed him to contribute significantly to a range of projects in basic science and health. As Chief Science Officer of SimBioSys, Inc., he is excited to extend this line of research
to enable transformative cancer treatment.

Tyler Earnest
Director of Computational Medicine PhD Physics University of Illinois at Urbana-Champaign

Tyler has a long history of mathematical modeling as applied to biological systems. He is also well-versed in software development, 3D visualization, and GPU programming as applied to computational biology. His primary focus is on
conceiving, constructing, and validating new cancer and drug models.

Michael Hallock
Director of Technology Development MS Bioinformatics University of Illinois Urbana-Champaign

Michael has more than 10 years of experience in the software development and information technology fields. He has extensive experience developing software for scientific computing, high performance computing, and cloud computing.
He applies his extensive knowledge to work on advanced analytics software, focusing on back-end (database, server/client communication, database development, IT infrastructure, etc.) technologies, as well as working closely with
full stack developers. Additionally, he will provide software support for scientific development.

Anu Antony,
MD, MPH, MBA, FACS
Chief Medical Officer MBA Kellogg School of Management at Northwestern University, MPH Harvard School of Public Health, MD University of North
Carolina- Chapel Hill School of Medicine, Stanford University Medical Center, Memorial Sloan-Kettering Cancer

Dr. Antony is a Harvard, Stanford, and Memorial-Sloan Kettering Cancer Center-trained surgeon with 20 years of experience in breast cancer, including multiple leadership positions in Chicago as Professor and Vice-Chair of the Department of Surgery at Rush University, Co-Director of the Breast Cancer Service Line, and Chief of Breast Reconstruction at the Rush University Cancer Center, and Vice-Chair of the Breast Cancer Center at the University of Illinois at Chicago Hospital and Health Services. She is passionate about innovation in precision oncology and commercializing cutting-edge technology to bring it directly into the hands of physicians and patients. Her interest in science and medicine began at UNC-Chapel Hill where she graduated with distinction in Chemistry. After graduating with honors at UNC-Chapel Hill School of Medicine, she became intrigued with medical device innovation during her general surgery and plastic surgery training in silicon valley at Stanford University Medical Center. She furthered her education and training during an oncologic reconstructive surgery fellowship at Memorial Sloan-Kettering Cancer Center, a Masters in Biostatistics and Clinical Outcomes at the Harvard School of Public Health, and an additional research fellowship training at Massachusetts General Hospital/Harvard Medical School. Recognizing the benefits of dovetailing science, medicine, and business, she completed an MBA at the Northwestern-Kellogg School of Management. Dr. Antony has worked in government and private sectors where she actively treated cancer patients, co-led a multimillion dollar NIH program grant as co-PI studying stem cells in a primate model, actively publishes, lectures nationally and internationally, and has served as Chair and President of several regional and national professional societies and conferences.

Tim Foley
Vice President, Business Development MBA, Kellstadt Graduate School of Business at DePaul University with emphasis on Applied Economics and Strategy, Execution, and Valuation

Charged with partnering initiatives to further our mission of empowering precision cancer care, Tim has joined as our VP of Business Development and comes armed with over 20 years in healthcare BD having led transaction teams at both Takeda and Astellas. Tim’s most recent focus is on helping health tech startups navigate the partnering paradigm. Cancer has had a large impact on his personal life leaving him impassioned to unlock new-generation solutions aimed at radically improving outcomes for tomorrow’s patients.

Tricia Carrigan,
PhD SVP, Precision Medicine PhD

Dr. Tricia Carrigan is an accomplished Biopharmaceutical and Diagnostic Executive with over 24 years of experience across the biomarker discovery- companion diagnostic-drug development and commercialization spectrum. She specializes in Companion Diagnostics (CDx) Strategy & Commercialization, drug development programs, early and late stage drug licensing, Oncology, Women’s Health, Cardiovascular, and Hematology. She has an international experience in assay implementation/development for Phase I-III trials, external innovation and business development/partnering in EU and Asia- Pacific markets.

Eduardo Braun, MD
Head of Clinical Affairs
MD, Rio de Janeiro School of Medicine, RUSH University Medical Center
Eduardo Braun, MD earned his medical degree at the Federal University of Rio de Janeiro School of Medicine. He completed his Fellowship in Hematology/Oncology, and his Residency in Internal Medicine at RUSH University Medical Center in Chicago. He is board certified in internal medicine, medical oncology and hematology.
Dr. Braun actively participates in lung cancer, breast cancer and lymphoma research and his work has been published. He is an active member of the American Society of Clinical Oncology, American Society of Hematology and the International Association for the Study of Lung Cancer.
Dr. Braun practices in Valparaiso, Chesterton, Hobart and Westville, Indiana.

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