Mandal, Santosh K.

Abstract Organometallic rhenium compounds have become powerful anticancer agents that show possibilities as a substitute for traditional platinum-based medications. While platinum-based chemotherapeutics like FOLFIRINOX and cisplatin are frequently used to treat pancreatic ductal adenocarcinoma (PDAC), they have a number of side effects, such as ototoxicity, neurotoxicity, nephrotoxicity, and peripheral neuropathy. Hepatotoxicity, cardiotoxicity, gastrointestinal toxicity, cytopenias, anaphylaxis, pain, alopecia, anorexia, cachexia, and asthenia are other commonly reported adverse effects. However, ligands based on rhenium have been shown to preferentially cause cytotoxicity in cancer cells while avoiding harm to healthy cells. This suggests that rhenium could be a safer and more effective cancer treatment option. Different rhenium compounds with different ligands have been produced by Mandal et al. for a range of medicinal uses. In this work, we assessed the therapeutic potential of tricarbonylperrhenato(bathophen)rhenium(I) (PR-6) in PDAC. The cytotoxic effects and IC50 value of PR-6 were assessed in the metastatic pancreatic cancer cell line AsPC-1 using the MTS assay. The IC50 value for PR-6 in AsPC-1 cells was determined to be 5.85 µM. PR-6 treatment significantly inhibited cell growth, migration, and survival at the IC50 concentration, with a post-treatment survival rate of 2.3 ± 3.97%. Furthermore, PR-6 treatment led to the downregulation of phosphorylated MEK (pMEK) and phosphorylated P38 (pP38) protein expression, indicating its modulatory effect on the MAPK signaling pathway. According to our research, PR-6 has a great therapeutic promise for treating pancreatic cancer and efficiently alters the tumor microenvironment in PDAC cells. Citation Format: Ishita Saha, Cecilia Parpinelli, Birsen Varisli, Santosh Mandal, Santanu Bhattacharya. Anticancer efficacy of tricarbonylperrhenato(bathophen)rhenium(I) organometallic compound in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 985.

Abstract Cancer is a public health crisis affecting approximately 19.3 million globally, annually. Lung cancer has the highest percentage of incidence and is responsible for 27% of cancer-related deaths. The prevalence of lung cancer worldwide led us to investigate differential gene expression in lung adenocarcinoma and small cell lung cancer cell lines in comparison to a healthy lung cell line. We also investigated the effect of lung tumor microenvironment to bone marrow derived pluripotent mesenchymal stem cells (PMSC) and tumor associated macrophages. This research involved cancer and healthy cell line culture with appropriate medium. Whole transcriptomic and small non-coding RNA sequencing and analysis by Ingenuity Pathway Analysis (Qiagen, USA), Quantitative RT-PCR and ELISA assays. We further studied morphological changes and differential gene expression in extracellular vesicles(exosomes) isolated from the TAM and TME exposed PMCs by atomic force microscopy and RNA sequencing techniques. The results of our investigation showed differential gene expression and novel core canonical pathways in the lung cancer cells, TME exposed TAM, and PMSC. We also observed morphological changes in TME derived exosomes from TAM and PMSC. RNA sequencing results showed differential gene expression of both coding and non-coding RNAs including tRNA fragments. Thus, our findings of this investigation led to identification of multiple cancer related genes and small non-coding microRNA, long non-coding RNA, and tRNA fragments which will have potential diagnostic and therapeutic target value that demands further future research. Acknowledgement: This research is supported by a grant from US NIH-NIGMS- 5T34GM100831-08 and US-NIH Grant# U 54 MD007597-31-5959. Citation Format: Hirendra N. Banerjee, Joseph Hedley, Cheslsey Aurelus, Narendra Banerjee, Kuldeep Rawat, Quentin Reaves, Shennel Brown, Darla Gilmartin, Makieyah Liverman, Jazmine Cuffee, Elizabeth Cagle, Erik Armstrong, Brent Lake, Santosh Mandal, Somiranjan Ghosh, Stephen Beebe, Kamal Asadipour, Christopher Krauss, Santanu Bhattacharya, Tanmay Kulkarni, Zahidur Abedin. An investigation to study differential gene expression of lung cancer cells, tumor associated macrophages, and bone marrow derived mesenchymal stems cells in the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5477.