Abstract 3350: The pan-quadruplex drug QN-302 targets up-regulated genes in pancreatic cancer and in other cancer types and correlate with poor patient prognosis

Abstract We have previously disclosed (Ahmed et al, ACS Med Chem Lett, 2020) a novel small molecule G-quadruplex binding compound, QN-302, that is highly potent in pancreatic ductal adenocarcinoma (PDAC) cells and in several in vivo models for this disease. QN-302 was invented at University College London UK and has been subsequently developed by Qualigen Therapeutics Inc. It was cleared by the FDA in August 2023 for clinical evaluation and is currently in a Phase 1 clinical trial at select oncology centers in the USA. Genes that are significantly down-regulated by QN-302 are mostly up-regulated genes in human PDAC. We report here that some of these genes are also up regulated in other cancer types, whose expression frequently correlates with poor patient prognosis. We have used human cancer data from https://www.proteinatlas.org which contains pathology information based on mRNA and protein expression data from 17 different forms of human cancer, together with millions of in-house generated immunohistochemically stained tissue sections, images and Kaplan-Meier plots showing the correlation between mRNA expression of each human protein gene and cancer patient survival. We have revisited the RNA-seq data for QN-302 in PDAC MIA-PACA2 cells exposed to QN-302 for 24 hrs. (GSE151741 at https://www.ncbi.nlm.nih.gov/geo/) in detail and now identify a small group of eleven down-regulated genes, all with >3-fold expression changes. Interestingly all these genes and their gene products have been previously identified as playing a role in human PDAC (they also have varying roles in other cancer types). Some have been validated as anticancer targets. 10/11 of these genes (https://www.proteinatlas.org/) have been previously reported as being over-expressed in significant fractions of large (>150) groups of human cancer patients from The Cancer Genome Atlas (TCGA) project. Members of the PDAC susceptible gene panel are mostly disfavored in prostate, lung and breast cancer. However, the patient data does not discriminate between cancer sub-types nor does it show resistant data. They are especially favored in colorectal, liver and renal cancers, suggesting that QN-302 may have anticancer effects in these cancers as well as in PDAC. We also do not exclude the strong possibility that each cancer type also has its own group of G-quadruplex containing genes that are sensitive to QN-302. Citation Format: Stephen Neidle, Ahmed A. Ahmed, Tariq Arshad. The pan-quadruplex drug QN-302 targets up-regulated genes in pancreatic cancer and in other cancer types and correlate with poor patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3350.