SACM - United States of America
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Item Restricted The Role of HBP1 in Colitis and Triple Negative Breast Cancer(2023-04-03) Bogis, Ahlam Mukhtar; Yee, AmyThere is a lack of clinical biomarkers and genetic models of ulcerative colitis (UC). Current clinical treatments are focused mainly on symptomatic relief through the use of anti-inflammatory therapy. There is unmet need to find clinical biomarker and therapeutic intervention targeting the etiology of the disease. The data from patients with colitis showed there is a decreased in HBP1 expression. Also, our analysis shows that 50% of HBP1-/- mice spontaneously develop moderate to severe colitis, and 25% of HBP1-/- mice develop CAC or dysplasia in conjunction with colitis. Furthermore, HBP1-/- mice are more susceptible to DSS-induced colitis and have decreased survival in compared to the wild type. We found a significant increase in the formation of organoids from HBP1-/- mice relative to WT, which suggest increased colonic stem-cell response to Wnt ligands in HBP1-/- mice. HBP1 is a negative regulator of HBP1 and our RNA seq analysis revealed activation of miR-155 gene set in the HBP1-/- colon. Most importantly, the immune component in the colon is altered by HBP1 deletion. Together, our data that HBP1-/- mouse could be used as a potential preclinical model for colitis. Given the role of HBP1 in altering the colonic resident immune cells, we thought to study the role of HBP1 in tumor microenvironment. We found loss of HBP1 helps in TNBC result metabolic reprogramming of the tumor microenvironment and Warburg like effect and increased in lactate production and consequently altered the tumor associated immune cells in tumor microenvironment into more immune suppressive environment. Both of my projects proposed immune system alteration in TNBC resulting from HBP1 dysfunction and also immune cell infiltration in the colonic epithelium of HBP1-/- mice.19 0Item Restricted An Economic and Regulatory Analysis of Breast Cancer Drugs Approved by the US Food and Drug Administration(2023) Althomali, Abdullah; Vazquez, Enrique SeoaneBreast cancer is the most common cancer among women and the leading cause of cancer death among women worldwide. The pharmacological options for breast cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy, which are used for the prevention or treatment of breast cancer. This study assessed trends in FDA approvals and prices at the market entry of new drugs indicated for breast cancer in the period 1980-2022. The study also evaluated the factors associated with the price of the new breast cancer drugs at market entry. Material and Methods Regulatory data were collected from the FDA website, and the wholesale acquisition cost (WAC) at market entry from the IBM Micromedex Redbook. We estimated the cost per year or per treatment as defined on the FDA-approved drug label. The WAC was adjusted to 2022 dollars using the consumer price index. Descriptive statistics and generalized linear model regression analysis were conducted. Results As of December 31, 2022, the FDA approved 30 drugs including 23 new molecular entities and 7 new biologics, with 60 indications for different stages of breast cancer and 71 indications for other diseases. The FDA approved 22 (75.9%) drugs using a priority review designation and 5 (17.2%) were granted orphan designation. The median of the inflation-adjusted WAC treatment cost at market entry was higher for drugs approved for advanced and metastatic stages of breast cancer (n=42, median=$88,019, interquartile range (IQR)=$148,969) than those approved for early stages of breast cancer (n=18, median=$51,150, IQR=$141,203). The price of breast cancer drugs at market entry was positively associated with the stage of cancer (specifically, stage 4), approval date, priority review designation, and HER2-positive or TNBC breast cancer subtypes. Conclusions The FDA approved a large number of drugs indicated for the treatment of different types of breast cancer in the period 1980-2022. The CPI-adjusted WAC treatment cost at market entry significantly increased in the period of analysis. Drugs for advanced cancer states, priority review designation, and for specific cancer subtypes were associated with higher treatment costs.29 0