•    Even after over 10,000 robotic prostatectomies, prostate cancer surgery still remains extremely complex and challenging

•    As it is for all forms of surgery there is a significant learning curve 

•  Initial outcomes maybe worse and improve with experience

• The learning curve is steep and dependent on many factors

•    The robot itself does not make the outcome automatically better

•    Outside of patient characteristics the experience of the surgeon is the primary determinant of patient outcomes

The deposition and removal of DNA and histone modifications depends on the availability of specific metabolites, suggesting that cellular metabolic pathways may dynamically regulate chromatin modifications and gene expression. However, whether changes in metabolic flux can influence cell fate decisions is poorly understood. Dr. Finley’s research focuses on understanding how cell type-specific metabolic profiles contribute to the establishment and regulation of cell identity. In her seminar, Dr. Finley will present recent work illustrating how the metabolic wiring of embryonic stem cells promotes an open chromatin landscape and the maintenance of pluripotency. These results reveal that intracellular metabolic pathways play a mechanistic role in the transcriptional and epigenetic state of stem cells.

For Research Use Only. Not for use in diagnostic procedures.
 

Acral lentiginous melanoma (ALM) is a rare sun-shielded melanoma subtype associated with worse survival than cutaneous melanoma (CM), a more common form of skin cancer linked to exposure to ultra-violet (UV) light. In order to better understand the genomic landscape of ALM with the goal of identifying novel therapeutic strategies, we performed comprehensive genomic and transcriptomic analysis of 37 tumors from 34 clinically well-annotated, histopathologically qualified ALM patients. For all samples with available analytes, whole exome sequencing, long insert whole genome and mRNA sequencing was performed. Bioinformatics tools and workflows were used to identify somatic point mutations, indels, copy number alterations, structural variants, and to perform gene expression analyses. The overall mutation burden (SNV) was variable, with a median of 123 SNVs (range of 2-2449), including 16 samples with < 100. Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures. Only 38% of patients demonstrated driver BRAF/NRAS/NF1 mutations. Contrasting with CM, we observed PAK1 copy gains in 15% of patients, and somatic TERT translocations, copy gains, and missense and promoter mutations, or germline events, in 41% of patients. We further show that in vitro TERT inhibition has cytotoxic effects on primary ALM cells. Our study thus demonstrates the value of implementing a comprehensive sequencing and informatics strategy to understand the genomics of a disease and how such integrated analyses have the power to lead to identifying therapeutic strategies for patients. 

The detection of circulating molecular biomarkers is useful for monitoring pathogenic processes and response to therapeutic intervention1,2. In cancer, genomic and proteomic biomarkers are used to assess tumour sub-type and stage, and determine patient stratification. Research has shown that using a combined signature of multiple biomarkers can better account for patient and epidemiological heterogeneity, and provide a more accurate indication of patient health2. In addition, the desire to leverage minimally-invasive samples has necessitated the development of technologies that can profile biomarkers directly from biofluids such as plasma, serum, and urine. To address this need, we developed the FirePlex Technology platform, which allows for the sensitive and accurate multiplexed detection of protein analytes or miRNAs directly from a wide array of biological samples. The platform uses patented, multi-functional hydrogel particles that allow for in-well multiplexing and panel design flexibility.

For the detection of protein analytes, FirePlex immunoassays use high-performance matched antibody pairs that provide minimal cross-reactivity between individual analytes, up to 5 logs dynamic range, and single-digit pg/ml sensitivity, while requiring only 12.5 µl biofluid input. Similarly, the FirePlex miRNA assay can reliably detect miRNAs directly from as little as 10 µl of biofluid without the need for RNA purification. This assay utilizes single¬ step RT-PCR signal amplification with universal primers, thus leveraging PCR sensitivity while eliminating an independent reverse transcription step and mitigating amplification biases introduced by target¬-specific qPCR.  

FirePlex assays are validated across a wide range of biological samples including plasma, serum, urine and cell culture supernatant. The 96-well plate assay format enables high-throughput sample screening with readout on standard flow cytometers, thereby omitting the need for complex and expensive dedicated instrumentation. Finally, the integrated FirePlex Analysis Workbench software enables rapid data analysis, visualization, and export, and includes key features such as standard curves as well as publication-quality heatmaps and graphs. 

Here we present data from studies using the FirePlex Platform to profile miRNAs in cancer. Together, the combination of multiplexed, high¬-sensitivity assays with powerful bioinformatics tools enables rapid discovery and validation of biomarker signatures from liquid and solid specimens.

The promise of precision and personalized medicine is rooted in accurate, highly sensitive, and specific disease biomarkers. This is particularly true for cancer-a disease characterized by marked tumor heterogeneity and diverse molecular signatures. Although thousands of biomarkers have been described, only a very small number have been successfully translated into clinical use. Undoubtedly, there is need for rapid, quantitative, and more cost effective biomarkers for tumor diagnosis and prognosis, to allow for better risk stratification and aid clinicians in making personalized treatment decisions.

Mr. Getson, a USA immigration lawyer, focuses on EB-1A(Extraordinary ability) and NIW (National Interest Waiver) cases, the primary categories in which scientific researchers qualify for green cards in the U.S.  In this presentation for foreign researchers, Mr. Getson will explain how to plan ahead to avoid problems with your immigration status, and he will teach you how to maximize your chances of qualifying for a green card.

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of only 9%. Acquired drug resistance is a major factor that limits the effectiveness of chemotherapy. Exosomes, secreted membrane vesicles that range in size from 30–100 nm in diameter, released from epithelial cancer cells can promote drug resistance. However fibroblasts, not epithelial cells, make up the majority of the tumor bulk in PDAC. Despite the long-standing recognition of the prominence of the fibroblasts in PDAC, the mechanisms through which fibroblast-derived exosomes may contribute to chemoresistance following exposure to chemotherapy have not been studied. A molecular-level understanding of possible fibroblast-driven mechanisms of chemoresistance is essential for the development of more effective treatment strategies.

Here, we show that CAFs exposed to chemotherapy play an active role in regulating the survival and proliferation of cancer cells through the hypersecretion of chemoresistance-promoting exosomes. We found that CAFs exposed to gemcitabine (GEM), the most widely used adjuvant therapy for PDAC, increase the release of exosomes. We utilized miRNA-SEQ analysis to identify miRs that were significantly increased in the exosomes of GEM-treated CAFs compared to treatment naïve CAFs and WT pancreatic fibroblasts. Five out of the top 10 hits were miRs that target PTEN. We utilized GW4869, a compound that inhibits exosome secretion, to functionally show in vitro and in vivo that blocking exosome release from GEM-treated CAFs reduces chemotherapy resistance in PDAC cells through restoration of PTEN expression. Collectively, these findings elucidate the role of CAF-derived exosomes in regulating PDAC chemoresistance and suggest that therapeutic strategies design to inhibit exosome release may lead to improved patient response.

The detection of CTCs has been used as useful biomarkers in prognosis and monitoring therapeutic response of patients with metastatic cancer. However, during the course of cancer therapy, CTCs have undergone epithelial-mesenchymal transition (EMT) (i.e., EMT CTCs) and the current FDA-approved technology is unable to detect such EMT CTCs. Using new technologies such as antibody against cell-surface vimentin (CSV) exclusively expressed on EMT CTCs, we are able to detect EMT CTCs from breast, colon, and prostate tumor types and monitor disease progression and predict the prognosis. This presentation will briefly review the current status of CTC detection, the detection technology and clinical utility of CTC. The challenges of the current technology and new technology in determination of CTC will be addressed. The detection of EMT CTCs especially CTC with molecular profiling for cancer diagnosis, monitoring therapeutic responses, predicting prognosis, and guiding personalized therapy will be discussed. Detection of CTCs and molecular characterization as one of the liquid biopsy approach may serve as an instrumental role for noninvasive approach in personalized cancer medicine. 

The analysis of circulating biomarkers in a patient’s blood holds significant potential for early disease detection and disease monitoring. Circulating DNA is the most commonly studied biomarker in the context of Liquid Biopsy research. However, in the last couple of years, free-circulating RNA has gained more attention for biomarker analysis and interpretation.

In this webinar, we will discuss the different types of circulating RNA biomarkers studied in Liquid Biopsy samples. A special focus will be given to the challenges and solutions for circulating RNA isolation.

In order to expand the treatment options of cancers driven by oncogenic RAS, new cell surface targets need to be identified and characterized. Here, we describe mass spectrometry based phenotyping of the KRASG12V cell surface using MCF10A-KRASG12V as a cell line model of constitutively activated KRAS. Extensive view of the MCF10A-KRASG12V surface proteome was achieved by applying concurrently targeted hydrazide-based cell surface capturing (CSC) technology and global shotgun membrane (GSM) proteomics. Our combined approach revealed 666 plasma membrane proteins unique to the MCF10A-KRASG12V cell surface. Of these, 104 were cell surface glycoproteins identified by CSC technology while 562 cell surface proteins were identified using GSM proteomics. K-Ras was exclusively identified by GSM proteomics in the membrane fraction of MCF10A-KRASG12V cells and subsequently cross-validated by Western blot (WB) analysis. Subtractive proteomics, spectral counting-based based quantitation of changes in protein abundances, and Ingenuity Pathway Analysis showed that this investigation reliably revealed expected K-Ras induced changes at the surface of MCF10A-KRASG12V cells as well as alterations in cell surface protein expression with very little prior information. This analysis uncovered a subset of eight proteins identified exclusively at the cell surface of MCF10A-KRASG12V cells by both CSC and GSM technologies. Of these, two were further cross-validated using immunofluorescence and WB analysis. Furthermore, scanning electron microscopy and functional cell assays showed extensive changes at the KRASG12V cell surface consistent with widespread epithelial to mesenchymal transformation (EMT). Taken together, this dataset greatly extends the known molecular phenotype of the MCF10A-KRASG12V cell surface and reveals the important role of EMT in the pathophysiology of the KRASG12V driven malignant transformation in MCF10A- KRASG12V model cell line.

The role played by inflammatory hypoxia in biology and treatment of solid tumors will be reviewed.  The opportunity to enhance all forms of current anti-tumor therapies through tumor re-oxygenation therapy using hyperbaric oxygen will be presented. 

Colorectal cancer (CRC) is the third most common cancer among Americans, and the second deadliest. Its pathogenesis results from an interplay between environmental factors that influence biological behavior of colonic stem cells, and the genetic makeup of susceptible individuals. Activation of stem cell proliferation from this interplay eventually yields adenomatous polyps, which if not removed after detection through an effective screening program, may further progress to cancers that may metastasize and affect survival. This normal-to-polyp-to-cancer process appears to occur at different initiation ages and progresses at different rates among various races in the United States, with African Americans demonstrating the highest incidence and mortality for CRC among all races. Compared with Caucasians, African American CRC patients tend to present at a younger age, have a more proximal cancer, present with more advanced stage, and show shortened survival. In parallel, African Americans demonstrate higher risk adenomatous polyps and more proximally-located polyps than Caucasians as the precursor lesions to CRC. There are likely multifactorial factors that contribute to this disparity, including socio-economic, health insurance, and educational factors, CRC screening utilization, diet, obesity, and microbiome makeup of the colon, tobacco utilization, use of NSAIDs and hormone replacement therapy, and differences in biology of the tumor and/or metastasis. Increasing CRC screening rates towards 80% utilization or greater for African Americans suggests that this disparity may be lessened or disappear. Other strategies such as enhanced patient and physician education and patient navigation for colonoscopy may also reduce the disparity. The U.S. Multi-Society Task Force on Colorectal Cancer, for the first time as of July 2017, endorsed lowering the screening age for African Americans from 50 years of age to 45 years of age, an age where the proportion of CRCs below age 45 years matches the proportion of CRCs among Caucasians below 50 years of age. Employment of these and other strategies may further mitigate the observed disparities.

We developed two computational methods, CARE and TIDE, to predict response and resistance to targeted therapies and immunotherapies. CARE infers gene signatures of targeted therapy response based on finding genes interacting with the drug target genes from CCLE, CGP and CTRP compound screens on cancer cell lines. CARE shows superior performance on predicting patient response to targeted therapy and chemotherapy, and predicted novel synergistic drug combinations that were experimentally validated. TIDE infers tumor immune dysfunction and exclusion based on finding genes from TCGA gene expression data that interact with tumor infiltrating CD8 T cells to impact patient survival. Interestingly, the TIDE signatures computed from clinical data without immunotherapies can reliably predict the clinical response of melanoma patients for both anti-PD1 and anti-CTLA4 therapies, with higher accuracy than mutation load and other biomarkers.

Pancreatic cancer is one of the “deadly” cancers, defined as those with a 5-year relative survival rate of less than 50%.  Although ranking 12th in terms of incidence, it is on track to become the second leading cause of cancer deaths by 2020.  The Pancreatic Cancer Action Network (PanCAN) set a goal of doubling survival by 2020, identified 5 specific challenges that need to be addressed, and initiated approaches to contribute to their solution.  There are not enough researchers or research, the clinical trial enrollment rate is too low, clinical trials need to be streamlined and focused, there is insufficient public awareness, and most patients are seen in the community setting where there is little experience with the disease.  Through advocating for government resources, the NCI allocation to pancreatic cancer has increased 5-fold since 1999, with several new research initiatives that resulted from the passage of the Recalcitrant Cancer Research Act in 2013.  Patient Central associates served more than 33,000 patients and families last year, providing disease and treatment information, support resources, and clinical trial searches.  The Patient Registry collects information from individual patients, learns best practices, and disseminates information on topics such as the use of pancreatic enzyme replace therapy to the scientific community.  The Know Your Tumor ® initiative has enrolled more than 1300 patients from across the US, and delivered almost 700 reports thus far detailing the results from genomic and proteomic analysis of tumor tissue with treatment options based on the molecular profiling and consideration of treatment history.  These results indicate that 25% of pancreatic cancer patients have “actionable alterations” that indicate a targeted therapy, and that the median progression-free survival of patients that utilize a report-directed targeted therapy increased by 46% over those with no highly actionable alteration.  The clinical trial landscape in pancreatic cancer has changed over the past 5 years, with a doubling of those trials that test a targeted therapy and an increase in trials for recurrent disease.  The accrual of pancreatic adenocarcinoma patients to clinical trials increased from 3.8% in 2011 to 4.2% in 2014; this is at least in part attributed to increased awareness of clinical trials through PanCAN’s Clinical Trial Finder (12% of those who access this service enroll in a clinical trial) and Know Your Tumor ® initiatives (21% of participants enroll in a clinical trial).  PanCAN is initiating Precision PromiseSM , a clinical trial and research platform with the mission of continuously and rapidly evaluating novel treatment options for pancreatic cancer.  Public awareness of the disease is raised with a volunteer presence in 90 communities throughout the US and leadership in the World Pancreatic Cancer Coalition.  A comprehensive approach to the disease, through Government Affairs, Research Grants & Clinical Initiatives, Patient Services, and Community Engagement, has resulted in significant advances on multiple fronts, helping to propel the field towards achieving the goal of doubling survival by 2020 and using that as a platform for continued and sustained improvements in the years to come.

Nanopore sequencing has enormous potential for application to cancer, but specifically offers advantages into two main arenas, epigenetics and structural variation. Methylation is well-known to be altered in cancer as compared to normal tissue, but how these changes arise and what patterns they are comprised of is only recently being explored. We have demonstrated the ability to sequencing phased methylation patterns in cancer versus normal samples over >5kb fragments, illustrating the potential of this technique.  Using methylation calling, we can probe the heterogeneous nature of the cancer epigenome, as well as the changes which occur between normal and cancer samples.  

Structural variants comprise a significant fraction of mutations in cancer, e.g. 50% of pancreatic cancer mutations.  Unfortunately, limitations of conventional, short-read DNA sequencing technologies make it difficult to detect these variations which often lie in repetitive regions. Nanopore sequencing can overcome these limitations, allowing more in-depth study of SVs and phased SNVs. We applied solution-phase hybridization capture to target SV hotspots in pancreatic cancer samples with long-read sequencing.  We also demonstrate that with signal level analysis, we can call SNPs and SVs in the same sample.

Immunotherapy: An unprecedented opportunity

-Long-lasting/curative treatments
-Lower side effects
-Wide applicability
-Natural mechanism of action
-Locally produced T cell therapies
    -jobs
    -talent
    -innovation
    -intellectual property
    -cost control

Exosomes are nano-scale lipid membrane-enclosed extracellular vesicles that form in the cellular endosomal system but are released outside the cell. These virus-sized “fat balls” (which also contain numerous proteins, nucleic acids, and other metabolites) are capable of extraordinary autocrine/paracrine and endocrine signaling functions on recipient cells that are proximal to, and distal from, the cells of origin. We have studied several areas of tumor-derived exosome impacts on recipient cells, whether those recipients are the tumor cells themselves (brain tumor cells, in this case), immune cells (lymphocytes in particular), and neighboring normal cells (glial cells/astrocytes). The common denominator in all of these cell/tumor exosome interactions is that the outcomes generally benefit the tumor, but that can be dependent on the context. In this talk we will describe our experiences with glioma exosomes 1) as cancer vaccines (immune stimulation!), but also as 2) agents of cancer immunosuppression (as mentioned, context-dependent), and as 3) drivers of inflammatory responses that seem to aid and abet tumor growth (and may turn normal cells into cancer cell progenitors). As opposed to a “unified field theory”, we instead offer the concept that cellular context and timing of arrival determine the downstream effects of glioma exosomes on the cells that encounter those fat balls.

The “R2G2” (B6;129-Rag2tm1FwaIL2rgtm1Rsky/DwlHsd) knockout mouse is the latest advancement to provide an alternative option in the highly immunodeficient mouse model category for oncology, immunology and other biomedical research communities. This model was generated by backcrossing an IL2rg (common gamma) knockout model to a RAG2 (recombinase activating gene) knockout model. The resulting mouse lacks various cytokines including IL-2, IL-4, IL-7, IL-9 and IL-15. In addition, this model lacks B cells, T cells, NK cells and has a deficiency in lymphocyte development. The R2G2 mouse model is not only ultra immunodeficient, but provides a model that is less leaky and more tolerant to gamma radiation than traditional SCID models. Herein we describe the development and characterization of the R2G2 mouse model, which includes breeding history, growth curve, complete blood count and serum chemistry, flow cytometry, tumor growth and radiosensitivity.

Natural killer cells (NKs) are lymphocytes of the innate immune system that target and kill cancer cells through the secretion of lytic granules containing granzyme B and perforin. This process requires the formation of a specialized cell-cell interaction region called the immune synapse (IS). Previous reports have established that the formation of the IS largely rely on sequential rearrangement of actin filaments within NKs. In contrast to the well-characterized configurations of actin filaments in NKs during the lytic process, there is a gap of knowledge regarding the organization and role of the tumor cell actin cytoskeleton during NK attack. 

In this project, we showed that the actin cytoskeleton of NK-resistant tumor cells accumulates at the IS. Using the high-throughput The ImageStream®X MKII Imaging Flow Cytometer and applying specific masks and features, we found that the majority of cells belonging to the resistant cell lines respond to NK cell attack by local and fast accumulation of actin near the IS. Furthermore, we showed that actin accumulation is associated with autophagosome clustering at the IS which drives the degradation of granzyme B inside the target cell. Moreover, our data suggest that the ability of cancer cells to respond to NK attack by fast actin remodelling is associated with their EMT status. We extended these data by analysing a large panel of breast cancer cells and showing that mesenchymal cells are significantly more resistant to NK-mediated cell death as compared to epithelial cells. 

Together our data demonstrates that resistant breast cancer cell lines respond to NK cell attack by a tumor actin remodelling and accumulation at the region of the IS. Targeting actin signalling pathways and regulators involved in these processes allowed to increase the susceptibility of resistant cells to NK cell-mediated cell death. 

More and more decisions will center on the ability to molecularly characterize a disease. So the molecular diagnostic laboratory will have a pivotal role. What does that look like? Will we be able to maintain an environment where we have academic laboratories doing a good chunk of innovation and development that then can get translated into either reference laboratories or tests being done at local laboratories within the academic core and even community hospitals? The ecosystem that exists now encourages innovation to happen quickly and get those tests quickly into the hands of the clinical laboratories and make them accessible to patients. So the question is can we maintain this ecosystem when we overlay regulatory pressures, and financial or reimbursement pressures.

The first small molecule inhibitor of the molecular chaperone Heat Shock Protein 90 (HSP90) was identified more than 20 years ago. Upon determination of the drug binding site and clarification of its mechanism of action, HSP90 was validated as an anti-cancer molecular target, robust preclinical activity was demonstrated, and the first clinical trials of an HSP90 inhibitor in cancer patients were initiated several years later. Since then, additional natural product and synthetic HSP90 inhibitors have been identified and many have been clinically evaluated. As a class, these inhibitors are ATP-competitive and inhibit the ATPase driven HSP90 chaperone cycle, causing degradation of HSP90-dependent proteins (termed clients), including many oncogenes, via the proteasome. While numerous clinical trials have been performed with HSP90 inhibitors and encouraging data have been obtained, no HSP90 inhibitor has yet received FDA approval. One consequence of HSP90 inhibition is upregulation of the cytoprotective heat shock response, a broad transcriptional response to proteotoxic stress that is regulated by the transcription factor Heat Shock Factor 1 (HSF1). HSF1 also mediates a cancer-specific transcriptional program. HSP90 is proposed to sequester HSF1 in unstressed cells, but there is little evidence to support this model. A better mechanistic understanding of the role of HSP90 in modulating HSF1 may facilitate improved clinical activity of HSP90 inhibitors. We recently showed that HSP90 binding to HSF1 depends on HSP90 conformation and is only readily visualized for the ATP-dependent, N-domain dimerized chaperone, a conformation only rarely sampled by mammalian HSP90. Further, we show that ATP-competitive, N-domain targeted HSP90 inhibitors disrupt this interaction, resulting in the increased duration of HSF1 occupancy of the hsp70 promoter and significant prolongation of both constitutive and heat-induced HSF1 transcriptional activity. Not only do these suggest a role for HSP90 in feedback regulation of the proteotoxic stress response, but this characteristic of current HSP90 inhibitors likely contributes to lack of robust clinical response and we are currently evaluating several strategies that target HSP90 inhibitor effects on HSF1 without impacting HSP90 inhibitor-mediated degradation of oncogenic clients. Finally, a consistent property of HSP90 inhibitors to concentrate in tumors and to remain for an extended time period compared to normal tissues has prompted the use of HSP90 inhibitors as intracellular delivery vehicles to direct and concentrate conjugated cytotoxic agents in tumor while sparing normal tissues. This strategy extends the potential clinical utility of HSP90 inhibitors in cancer and a Phase 1 trial of such an HSP90-drug conjugate is underway.

There has been a great deal of renewed attention in immuno-oncology over the last decade.   Therapies for cancer are being developed, approved, and administered that can either initiate, modulate, or enhance immune response to various cancers including metastatic cancer.  This presentation will examine the advantages of using RNA measurements of the tumor micro-environment to measure not only tumor-cell expression and related systems but also the immune response (if any) to the tumor.  We will examine evidence of pan-cancer immunogenicity by utilizing RNA-Seq data from The Cancer Genome Atlas (TCGA).   From this view, we will see direct evidence that immune response can vary by cancer type and vary from other potential biomarkers of immunogenicity including tumor mutational burden.  In particular, we will examine potential applications of immune subsystem-related biomarkers with ovarian cancer in prognostic areas such as predicting event-free and overall survival.  

Colorectal  cancer  (CRC)  is  the  third  most  commonly  diagnosed  cancer  and  is  the  third leading  cause of  cancer-related deaths in the western world.  The mortality from colorectal cancer in Caucasian American (CAs) has been declining, but the death rate continues to be higher in African Americans (AAs), maintaining the racial disparity. In addition, AAs more often present with CRC at advanced stages contributing to the lower five year survival rate. Hispanic-Americans (HAs) have significantly lower CRC incidence and mortality rates when compared with Non- Hispanic AA (NH-AA) and Non-Hispanic CA (NH- CA) populations. However, rates among HAs are significantly higher than those among residents of Puerto Rico and other Spanish-speaking countries in South and Central America. Furthermore, preliminary data and documented results show that for HA the age at presentation is lower and the stage of the disease is higher than that of AA and CAs. We hypothesize that various factors (i.e., familial, socioeconomic, environmental and dietary) may contribute to the underlying problem of colon cancer racial/ethnic health disparity. Also, it has been noted that the response to chemopreventive agents differ as to the biological/genetic heterogeneity of the tumors of NH-AAs, HAs and NH-CAs. Since chemopreventive agents exert their effect through a molecular target, this disparity would suggest differences at the genetic level. Therefore, the formulation and evaluation of chemopreventive/chemotherapeutic agents that address the issue of differential chemoresponse and chemoresistance is essential to survival. To study, in vitro and in vivo, the development of and chemo-responsiveness of therapeutic agents to colonic diseases in diverse populations, the availability of the appropriate cells (cell lines/organoids) and animal (PDX) models are critical. Our overarching goal is to assess racial and ethnic genetic/epigenetic dysregulations and associate these changes to chemoresponse and colon cancer racial disparity. The availability of these biological tools will facilitate overcoming differential incidence and outcome seen among racial and ethnic groups for CRC. To achieve this goal, we are generating and characterizing novel cell lines, PDXs and organoids derived from NH-CAs, HAs and AAs patients with colorectal cancer. Downstream use of these biological tools will assist our group and the scientific community at large in improving targeted personal cancer treatment. This research effort is inclusive of all and will benefit a diverse population.