Pancreatic ductal adenocarcinoma(PDAC) is a highly aggressive and common form of pancreatic cancer. Patients with PDAC have a less than 10% five-year survival rate. One factor contributing to the aggressive behavior in PDAC is hypoxia, or lack of oxygen. Hypoxia is deadly in healthy tissue whereas it promotes survival and drug resistance in cancer. This has led to a lack of treatment options for PDAC patients. Given that healthy tissue is not hypoxic, developing a hypoxia specific drug may provide novel therapies for PDAC patients. Here, a drug screen was conducted from an established Food and Drug Administration library to determine if previously discovered compounds had the ability to target hypoxic cells. One compound was identified in the initial screen, 3-methoxycatechol. Tests will be done to determine the mechanism of action and assess the toxicity of this compound. Research focused on identifying PDAC and hypoxia specific targets will provide additional therapeutic options for patients improving overall survival rates.

Medulloblastoma is the most commonly diagnosed aggressive brain tumor in children. There are four distinct subgroups of medulloblastoma with different molecular characteristics. One of these, Group 3 (G3), accounts for 25% of cases with a less than 50% 10–year survival. G3 tumors are characterized by MYC amplification or gain, which is a pathway that currently is not clinically targetable. Investigations of novel therapies to disrupt MYC activity are highly relevant for tumor biology. Recent studies have observed that Y-box binding protein 1 (YBX1) is overexpressed in medulloblastoma compared to normal cerebellum, with the highest expression in G3 tumors. Interestingly, research has shown that YBX1 and MYC can regulate one another at both the transcriptional and translational levels. Recent work identified a small molecule with potent YBX1 inhibitory activity, however, its effects in medulloblastoma have not been studied. We hypothesize that inhibition of YBX1 will target MYC activities and decrease growth of patient-derived cell lines. We treated multiple G3 patient-derived lines with single agent YBX1 inhibitor (SU056) and noted a dose-dependent decrease in growth. We further tested the stability of YBX1 in the presence of SU056. We observed reduced protein stability with treatment, suggesting potent inhibitor binding. We are currently evaluating the effects of SU056 combined with standard-of-care therapies, such as chemotherapy and radiation. Based on previous work using RNAi, we expect that SU056 will sensitize cells to chemotherapy and/or radiation. These novel combinations may correlate with fewer side effects and will improve quality of life in children with medulloblastoma.

Inflammatory Breast Cancer (IBC) is one sub-type of breast cancer (BC) that is the most aggressive form with a higher morbidity and mortality rate compared to non-IBC cancer cells. SUM149, a type of IBC cell line, is also considered a Triple Negative Breast Cancer (TNBC). Triple Negative Breast Cancer is negative in estrogen receptor, progesterone receptor, and HER-2/NEU receptor. It is a common aggressive type of breast cancer with a high malignancy rate and poor prognosis with a chance of developing cancer cachexia (Zhang, 2022). Current treatments such as local surgical excision and chemotherapy have proven to be ineffective due to the aggressiveness and high resistant rate of the cancer (Lin S, 2022). However, alternative chemotherapeutic remedies such as curcumin and gallic acid have been proven to reduce cancer cell growth and promote cell apoptosis. We hypothesize that treatment with curcumin or gallic acid will result in a decrease in cancer cell growth, metastasis, and cell apoptosis.

Human T-cell Leukemia Virus (HTLV), is a retrovirus of clade deltraretroviradae with two known sub-types (HTLV Type-1 and HTLV Type-2). HTLV-1 can development into an extremely aggressive blood cancer called Adult T-cell Leukemia/Lymphoma (ATLL) but HTLV-2 does not. Tax is a viral oncoprotein expressed from HTLV Type-1. The coding regions for Tax vary in HTLV-1 and type-2 in the predicted transcriptional activation domain. Tax recruits host activator and co-activator proteins to bind to the integrated viral promoter region of HTLV and rapidly activate viral gene expression, possibly being the cause of ATLL. The transcriptional regulator function of Tax in the host cell are not fully understood at this time. Exploring interaction surfaces of Tax with various host proteins involved may help us understand the basic transcriptional activation mechanisms that are manipulated by the HTLV-1. To investigate this, we purified type of Tax called Strep-Tax. Once the oncoprotein Tax is purified, it can be used with more advance techniques such as activity bead-binding assays and it will increase the reliability of the results.