Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by the characteristic lack of receptors such as human epidermal growth factor receptor-2 (HER-2), the estrogen receptor (ER), and the progesterone receptor (PR). Major concerns for side effects of commercial drugs and the emergence of drug-resistant cancer cells, has created interest in the use of naturally occurring substances that possess chemo-preventive and chemotherapeutic properties in cancer treatment. Rosehip (Rosa canina) extracts have traditionally been used as dietary supplements to relieve symptoms associated with diarrhea, gastritis, and rheumatoid arthritis are gaining interest as a potential chemo-preventative agent. Rosehip extracts prevent cell proliferation in breast, colon, and cervical cancer cells, as well as glioblastomas. However, the anti-proliferative and anti-migratory effects of these extracts in triple negative breast cancer cells have not been examined. This study investigated the efficacy of rosehip extracts in preventing cell proliferation, migration, and invasion in triple negative and luminal breast cancer cells. Treatment with rosehip extracts caused a decrease in cell proliferation and migration. Results from cell cycle and western blot analysis, as well as apoptosis studies demonstrated that rosehip extracts inhibited cell proliferation but did not promote apoptosis. Anti-metastatic effects were observed after exposure to rosehip extracts and pretreatment of these cell lines with rosehip extracts decreased the level of several protein classes associated with cancers. These data suggest that rosehip extracts are capable of decreasing TNBC cell proliferation, migration, and invasion by inhibiting multiple signaling pathways. Rosehip extracts also had a synergistic effect with Doxorubicin to prevent triple negative breast cancer cell proliferation. When combined with doxorubicin, rosehip extracts enhance the anti-proliferative and apoptosis effect of doxorubicin. These data demonstrate the enhanced effect of Doxorubicin with rosehip in the inhibition of cell proliferation. Taken together these results demonstrate Rosehip extracts may serve as an alternative or compliment to current chemotherapeutic treatment for triple negative breast cancer.  

Learning Objectives:

1.    Define the effectiveness of plant extracts in preventing triple negative breast cancer growth and migration.

2.    Explain current approaches to developing natural product development.

3.    Identify potential of natural products as adjuvant therapy for aggressive cancers. 
 

Summary: Cancer neoantigens are highly specific to the tumor, potently immunogenic and can be targeted by both vaccines and engineered cellular therapies. This talk will introduce the definition of cancer neoantigens, review the neoantigen source, and discuss the challenges of neoantigen discovery from tumor genomic sequencing data.  In addition, I will talk about a phase-I clinical trial design for neoantigen vaccine therapy at Mayo Clinic.

Background: Immune Checkpoint Inhibitors (ICI) and Chimeric Antigen Receptor T-cells (CAR-T) are the two major immunotherapies that have revolutionized cancer treatments. Despite the immense promise of immunotherapies in treating various cancers, there have been a wide range of responses from patients. The percent of US patients with cancer who are eligible for ICI drugs increased to 43.63% in 2018 however only 12.46% of these patients are estimated to respond to ICI treatments. CAR-T has reached revolutionary milestone in treatment of hematological malignancies. However, CAR-T has not been yet successful in treating solid cancers due to the limited repertoire of cell-surface antigens and its ineffectiveness of infiltrating into solid tumor tissues. Furthermore, CAR-T therapy is not tumor-specific. The surface proteins targeted by CAR-T to-date are also expressed on normal cells resulting in on-target off-tumor and even off-target toxicities. In addition, significant challenges have been mounting to overcome treatment resistance and to improve efficacy. Strategies such as the combination immunotherapies of existing agents have so far yielded more failures than successes in this effort. Therefore, we have reached a critical point where it’s essential to search for and develop the novel next generation immunotherapy agents. Cancer neoantigens are among the most promising novel agents. 
 
 
Learning Objectives: 

1.    Discuss the different types of tumor somatic mutations that are sources of neoantigens.

2.    Break down the bioinformatics approaches for neoantigen identification from genomic sequencing data.

3.    Discuss basic design for phase-I neoantigen clinical trials.

Across oncology applications, from research to molecular testing and pharmaceutical development, the ability to identify potentially actionable genetic alterations and exploit the molecular vulnerabilities of cancer is becoming increasingly difficult. Due to the sporadic nature of somatic cancers, the number of detected variants is exponentially growing, challenging scientists to confidently identify meaningful mutations that could influence or improve decisions in experimental design, at point-of-care, or in drug development.

In this webinar, we will introduce you to the Human Somatic Mutation Database (HSMD)—a new somatic database developed by QIAGEN that contains extensive genomic content relevant to solid tumors and hematological malignancies. Available as a web-based application, this expert-curated resource contains content from over 300,000 real-world clinical oncology cases combined with content from the QIAGEN Knowledge Base, providing gene-level, alteration-level, and disease-level information including clinically observed gene and variant frequencies across diseases. Users can easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant. In addition, users can interrogate a bibliography of over 150,000 variant specific PubMed articles and access individual summaries alteration-type specific information written by PhD scientists. 
 

Learning Objectives:

1. Discuss what content sources power HSMD.

2. Explain how to use and apply HSMD for multiple applications, including research, molecular testing, and pharmaceutical development.

3. Discuss when and where you can access HSMD.

Cells in their natural environment are surrounded by a complex extracellular matrix that provides structure and functional cues to the surrounding cells. Hydrogels can be used to approximate this environment for 3D cell culture, but require preparative work including hydrogel assembly, hydrogel optimization, and cell encapsulation. Learn how our fully ready-to-use TrueGel3D™ HTS hydrogel plates help you to quickly and easily establish 3D cell cultures for high-throughput screening and high content analysis. Data will be presented to show how these automation-compatible plates can be used for imaging 3D cultures in immuno-oncology, angiogenesis, neuroscience, and ADME/tox studies.

Learning Objectives:

1. Explain how TrueGel3D® HTS plates solve current limitations of 3D cell cultures for drug discovery.

2. Identify how to easily establish cocultures of tumor spheroids and T-cells in 3D using TrueGel3D® HTS plates

3. Evaluate performing high-throughput drug screen using TrueGel3D® HTS plates

The lack of diverse participation in clinical research and trials has been a long-standing national problem that has been brought to the forefront due to COVID 19. In cancer research less than 9% of clinical research participants are from historically marginalized and underrepresented race and ethnic groups, a significant difference from the nearly . The lack of diversity is closely linked to health disparities and the need for effective application of patient and community engagement. This interactive session, entitled Just ASk, will provide insights as to the causes for lack of diversity in oncology and clinical trials, its connections to cancer health disparities, and individual and systemic strategies to increase diversity and reduce disparities through community and patient engagement. 
 
Learning Objectives:

1. Explain the factors that impact lack of diverse participation in oncology clinical trials s and research and why diverse participation is critical to rigorous research. 

2. Describe individual and systemic strategies to engage patients and community in research toward increasing diversity in oncology research and reducing health disparities. 

Advances in cancer research have improved our understanding of the complex interactions between tumors, their microenvironment and the host immune response. The evolving research field of immuno-oncology focuses on an individual’s immune system as innovative treatment approaches to combat cancer. The goal of cancer immunotherapies is to initiate a self-sustaining cycle of cancer immunity, overcome tumor evasion mechanisms and promote conditions that favor immune protection. Immune checkpoint molecules have been identified as critical players in the regulation of NK cell- and T cell-mediated immune responses. Besides intact transmembrane proteins, soluble isoforms and variants of checkpoint molecules function as immune adjuvants or decoy receptors and may also influence efficacy of checkpoint modulator drugs. The systematic analysis of these soluble biomarkers and other key targets should help to shed light on all crucial features of cancer including the regulation of checkpoint pathways, tumor growth and metastasis to facilitate research for future immunotherapeutic treatments. Moreover, analyzing the protein cargo of cancer cell-derived exosomes and the levels of a broader set of immunomodulatory markers will allow researchers to further decipher the complex interplay of mediators implicated in cancer development and progression. 

This presentation will provide an understanding of Luminex xMAP-based multiplex immunoassay solutions (RUO) that enable the simultaneous detection of multiple soluble immune stimulatory and inhibitory factors, providing a more complete picture of cancer immunity in a blood sample, both on the transcript and protein level. 

Learning Objectives:

1. Outline immunoassay solutions to advance cancer research.

2. Discuss cancer-derived exosomes as novel class of biomarkers.

3. Break down immuno-monitoring approaches to characterize and understand key changes in the immune response to cancer.

4. Explain mRNA cancer biomarkers using Invitrogen™ QuantiGene™ Plex assays for multiplex, high-throughput gene expression analysis.

5. Explain protein cancer biomarkers using Invitrogen™ ProcartaPlex™ assays for multiplex protein analysis.
 

Data suggests that genetics comprises 42-58% of the prostate cancer risk. GWAS has found about 43% of the risk SNPs in Blacks and European Americans. Most of the SNPs that have been discovered are not associated with aggressive prostate cancer but are more common in men of African ancestry. The genetic variants account for the increased incidence of prostate cancer in Blacks and I posit that environment and namely social determinants of health account for the mortality disparity. We found that the rates of latent prostate cancer are 4-6 times lower in men of West African ancestry in Africa relative to both Black and White Americans. Further, I argue that the American environment itself accounts for the excess prostate cancer mortality seen in both White and Black Americans relative to Nigerian and other West African men. 

Learning Objectives:

1.    Identify the degree of the incidence disparity for Blacks.

2.    Identify the degree of the mortality disparity for Blacks.

3.    Discuss the degree to which the genetic SNPs are associated with younger age and increased risk of overall cancer.

One of the central tenants of biology is that our genetics—our genotype—influences the physical characteristics we manifest—our phenotype. But with more than 25,000 human genes and more than 6,000,000 common genetic variants mapped in our genome, finding associations between our genotype and phenotype is an ongoing challenge. Indeed, genome-wide association studies have found thousands of small effect size genetic variants that are associated with phenotypic traits and disease. The simplest explanation is that these genetic variants work synergistically to help define phenotype and to regulate processes that are responsible for phenotypic state transitions. We will use gene expression and genetic data to explore gene regulatory networks, to study phenotypic state transitions, to analyze the connections between genotype, gene expression, and phenotyope, and to explore how cancer-risk SNPs exert an influence on the disease risk that extends beyond one locus. We will show how networks can lead us to new approaches to identifying therapies and therapeutic targets. 

Learning Objectives:

1. Discuss gene regulatory networks and tools for their inference that use biological constraints.
2. Explain how changes in network structure correlate with the sex of the subject and their clinical outcomes.

In this webinar, we present a case study on Lynch syndrome (LS), a hereditary condition characterized by a high risk of colorectal cancer, endometrial cancer, and other neoplasia that typically manifests in the context of germline variants in DNA mismatched genes. 
To study whether other germline pathogenic variants of hereditary cancer genes are present in patients previously diagnosed with LS, the researchers analyzed a comprehensive panel of cancer-predisposing genes by NGS among 84 LS probands.

With this study as an example, we will illustrate how you can use your own data and public data to conduct translational research using 3 software solutions from QIAGEN.

Learning Objectives: 

1. Analyze how you can efficiently retrieve and process FASTQ data with accurate variant interpretation using CLC Genomics Workbench

2. Interpret how you can take a set of variants and rapidly assess sample variants for disease relevance and pathogenicity using QCI Interpret Translational

3. Describe how you can combine results and contextualize variant biomarkers with other public datasets using QIAGEN Ingenuity Pathway Analysis (IPA)

Effective immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of suitable tumor-specific antigens. To address this challenge, we have combined high-throughput flow cytometry with high-content cyclic immunofluorescence for the early identification of target candidates for cellular immunotherapy. Within this webinar, we aim to guide the viewers through our most recently published scientific findings[1] and related cutting-edge tools, ranging from the preparation of primary and xenografted tumor specimens to the comprehensive antigen screening and deep phenotyping.

[1] Schäfer, D., Tomiuk, S., Küster, L.N. et al. Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. Nat Commun 12, 1453 (2021). https://doi.org/10.1038/s41467-021-21774-4  

Learning Objectives:

1. Breakdown a problem of solid tumor CAR T cell therapies is that most identified tumor-associated antigens are also expressed in healthy tissue.

2. Explain how we systematically screened for PDAC CAR targets by high-throughput flow cytometry followed by high-content immunoflourescent imaging.

3.  Duscuss how CD318, TSPAN8 and CD66c were identified as potential targets for CAR T cell based immunotherapy of PDAC.

Background: Localized prostate cancer is notable for tumor heterogeneity, and immune heterogeneity within tumor versus benign areas. B7-H3, a member of the B7 superfamily, is highly expressed (relative to PD-L1 and PD-L2) in prostate cancer, and is associated with rapid biochemical recurrence, early metastases, and differential expression between tumor and benign prostate tissue.  Methods: Enoblituzumab (MacroGenics, Inc.) is an investigational humanized Fc-optimized B7-H3–targeting antibody that induces antibody-dependent cellular cytotoxicity (ADCC). Recently, in a Phase 2 single-arm neoadjuvant trial (NCT02923180) at JHMI, men with operable intermediate- and high-risk localized prostate cancer received enoblituzumab (15 mg/kg IV weekly x 6) prior to surgery. Prostate glands were harvested 2 weeks after the last enoblituzumab dose, and were examined for pathologic and immunologic endpoints. The co-primary outcomes were safety and PSA0 at 1 year post-op.  Results: A total of 32 patients were enrolled. Grade 3/4 drug-related adverse events occurred in 12% of patients; there was no surgical delay due to AEs. PSA0 at 1 year post-op was seen in 66% of men (95% CI: 48-80%). Median time to PSA recurrence was not reached (95% CI: 9.4 months – NE). Gleason grade group changes were significantly associated with treatment compared to 1:1 matched controls. Exploratory tumor microenvironment profiling by NanoString GeoMx spatial proteomics and PanCancer IO 360 mRNA expression analysis revealed evidence of post-treatment upregulation of CD8+ T cells, PD-1/PD-L1, and immune activation (granzyme B, IFN signaling, myeloid inflammation).

Learning objectives:

1. Discuss the Gleeson Score of prostate cancer and the microenvironment but also the high-plex, spatial profiling in pre-treated and post-treatment of B7-H3.

2. Break down the use of spatial proteomic detection, understanding the robust intratumoral induction (adaptive upregulation) of immune checkpoints, T cell activation, and myeloid inflammation in prostate cancer.

There is considerable research being conducting on the topic of health disparities.  It is important to understand why these health disparities exist as well as what is contributing to so many years of sustained health disparities. A cancer diagnosis and treatment outcome are downstream results; therefore, it is important to know what contributed on the front-end to develop a more systematic approach to achieve better health equity. This talk will discuss how history and different systems have contributed to social drivers of health.  These social drivers of health along with our current healthcare system are contributing to health disparities.  I will describe and discuss a few examples of cancer disparities.  Lastly, I will close with some tangible actions that individuals and organizations can take to improve health equity.

Learning Objectives:

1. Discuss the importance of understanding historical contributions to health disparities.

2. Describe the impact social drivers of health and our current healthcare system have on health disparities.

3. Provide action items to improve health equity.

COSMIC is the world’s largest and most comprehensive somatic mutations resource. COSMIC’s contents are manually curated by PhD-level experts from high-quality scientific literature and trustworthy cancer programs like TCGA and ICGC.

COSMIC’s trove of information about mutations and tumor samples (like disease type, demographic data and therapies) is collected, standardized and integrated to allow for flexible use. And its suite of tools lets researchers and stakeholders explore and interpret the information in ways complementary to their goals.

In addition to the core database, COSMIC boasts a range of specialized component projects that each offer a distinct dataset or view of the data, including a 3D interactive view of cancer mutations.

COSMIC is updated with new content and improved functionality three times a year. Our most recent release (v94) contains over 37 million coding mutations and detailed phenotypic & genotypic annotations of 1.4 million cancer samples.

Vital to precision oncology research activities, COSMIC is fully available through QIAGEN. (https://digitalinsights.qiagen.com/products-overview/cosmic/).

African American women face a lower risk of being diagnosed with breast cancer as compared to Caucasian-American women, yet they paradoxically face an increased breast cancer mortality hazard.  This breast cancer health disparity is due primarily to the occurrence of an early-onset “triple-negative” [estrogen receptor-negative, progesterone receptor-negative and Her2-negative] breast cancer phenotype prevalent in African American women less than 35 years of age.  This type of breast cancer is very aggressive, has a poor prognosis, fails to respond to conventional therapy, and stains positive for mutant-p53.   The etiology and biological basis of the triple-negative breast cancer phenotype in African American women is currently unknown but is likely to be multi-factorial. There are models that predict the intersection of disparities and the aggressive biology of breast cancer in African American women.  Some factors that probably play a role in the disparity are unsafe neighborhoods, access to healthcare, co-morbidities, reproductive factors, and socioeconomic statuses.  Another major factor that has been revealed as a primary driver of the high mortality rate of triple negative breast cancer is the high risk of recurrence and the development of chemoresistance to therapeutic drugs such as doxorubicin.  We will explore the role that these factors play in breast cancer health disparities as a way to reduce their influence on driving increased death rates.   

Learning Objectives: 

1. Define breast cancer health disparity.

2. List at least three risk factors associated with breast cancer health disparity in African American women.

3. Discuss the role that chemoresistance play in driving breast cancer health disparities.