https://openworks.mdanderson.org/sumexp22/1082/thumbnail.jp

Bae, Seong-Woo

Manning, Henry Charles

Mohanty, Ayushi

Pham, Cong-Dat

English

OpenWorks @ MD Anderson

AcknowledgementsCombined Drug Therapy ResultsFuture WorkColorectal Cancer (CRC)o 3rd most commonly diagnosed cancer & 2nd leading cause of cancer death in men and women combined in the U.S.o Each year, about 150,000 Americans are diagnosed with this disease and more than 50,000 die.o Symptoms include a change in bowel habits, diarrhea, constipation, discomfort in the abdomeno Treatments include Surgery, Radiation Therapy, Chemotherapy, Targeted TherapyIntroduction Materials & MethodsResultsCombined Drug Efficacy using EGFR and ASCT2 Inhibitors in Preclinical Models of Colorectal CancerAyushi Mohanty1,2, Seong-Woo Bae2, Cong-Dat Pham2, Henry C. Manning21Carnegie Vanguard High School; 2The University of Texas, MD Anderson Cancer Center, Department of Cancer Systems ImagingTargeted TherapyEGFRo Found at high levels in cancer cells which causes proliferationo Panitumumab is an EGFR inhibitor and is for treating metastatic colorectal cancerASCT2o Found at high levels in cancer cells which causes proliferationo Inhibitor of glutamine metabolism V-9302 and CDP selectively target the amino acid transporter ASCT2HypothesisCombination drug treatment using EGFR and ASCT2 inhibitors will lead to greater response in colorectal cancer compared to single-drug therapy.Illustration of cancer in body.V-9302BCA Protein Assayo Quantitate protein concentration of each sampleMonotherapy & Combined Drug Therapy (Cell Viability Assay)o Panitumumab TreatmentCell Number: 5000 cells/wellDose (ug/mL): 0.01, 0.1, 1, 10, 25, 50, 100, 500, 1000Incubation time: 48 hrso V-9302 TreatmentCell Number: 5000 cells/wellDose (uM): 0.001, 0.01, 0.1, 1, 5, 10, 25, 50, 100Incubation time: 48 hrsReferencesWestern Bloto Running & Transfer Conditiono Run 70V for 20 minutes until sample has run through the stacking gel. At that point run 150V for 30 minuteso The membranes were transferred (1.3A, 25V, 10 minutes)o Antibody: Phospho-EGF Receptor, EGF Receptor, ASCT2, Anti-GAPDH antibody, Anti-rabbit IgG HRP-linked Antibodyo Expand research by conducting further trials using varying doses and incubation timeso Use bioinformatics analysis and RNA & DNA sequencing data to characterize cell lines used in studyo Identify other treatment targets that may lead to greater efficacyo Comprehend the relationship between Western Blot results and sensitivity to drug treatmento Conduct combination therapy in in-vivo and clinical trials to use in patients as FDA approved drugI would like to thank all the Manning Lab members especially my mentor Dr.Seong-Woo Bae, as well as my family, for supporting me throughout myresearch.H. Charles Manning is a Cancer Prevention Research Institute of Texas(CPRIT) Scholar in Cancer Research and is supported by CPRIT RR200046.1. “Colon Cancer Awareness.” Texas Digestive Disease Consultants, 11 Mar. 2019 2. Cohen, A. S., Geng, L., Zhao, P., Fu, A., Schulte, M. L., Graves-Deal, R., Washington, M. K., Berlin, J., Coffey, R. J., & Manning, H. C. (2020). Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer. Translational oncology, 13(10), 100828.3. Schulte, M. L., et al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nature medicine, 24(2), 194–202 (2018).Combination treatment using Panitumumab and V-9302 as well as CDPPanitumumab1 ug/mL for DIFI, 1000 ug/mL for the others48 hrsV-9302 or CDP series50 uM48 hrsBCA Protein Assay Western BlotSingle Drug Therapy

Combined Drug Efficacy of EGFR and ASCT2 Inhibitors in Preclinical Models of Colorectal Cancer

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1082&amp;context=sumexp22

Combined Drug Efficacy of EGFR and ASCT2 Inhibitors in Preclinical Models of Colorectal Cancer

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