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According to GLOBOCAN’s 2020 report, in Pakistan, lip and oral cavity is the second most prevalent cancer with a low survival rate due to late detection and ineffective treatment regimens. To reduce ineffective treatment, this study aims to develop a cost-efficient in vitro drug screening platform using patient-derived primary cell lines to identify effective drugs against Oral Squamous Cell Carcinoma (OSCC) patients. Chemotherapeutic drugs to be screened were identified from NCCN guidelines as well as the local standard of care after oncologists from three tertiary care hospitals. These included 15 chemotherapeutic drugs along with 14 combinations. For this pilot study, tumor biopsies were collected, after relevant IRB approvals from consenting patients as part of the Oral Cancer Genomics Study project. Patient-derived primary cell lines were generated from tumor biopsies of 20 local OSCC patients recruited at Rehman Medical Institute and Hayatabad Medical Complex, Peshawar, Pakistan. Primary cell lines were derived from tumor biopsies within 30 minutes of resection and propagated till confluency using an optimized DMEM protocol. The readouts of our screen include cell viability, cell proliferation and cytotoxicity. This pilot screen presents a first of its kind dataset of the performance of drugs and drug combinations in primary cell lines derived from the tumors of local patients in Pakistan. This is not just an ideal platform to test novel and re-purposed drugs but also to develop into a service for personalized treatments, minimizing ineffective treatment and improving patient outcomes. Citation Format: Sabaoon Zeb, Khudeja Salim, Hina Zamir, Madina Shirdel, Momal Agha, Asma Qudrat, Sajjad Ahmad, Muhammad Faisal, Muhammad Atif Munawar, Muhammad Mushtaq Khattak, Mushtaq Ahmad, Zubbair Durrani, Faisal F. Khan. Minimizing ineffective treatment using an in vitro patient derived cancer cell screening platform for local oral squamous cell carcinoma patients in Pakistan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6316.

Micro-RNAs are small non-coding RNAs that are able to modulate the gene expression. Aberrant expression of micro-RNAs leads to different diseased conditions such as cancer. Head and Neck Squamous Cell Carcinoma (HNSCC) is the second most prevalent cancer in Pakistan and contributes to 9.1% of mortality annually due to late stage diagnosis and ineffective treatment. This research attempts to identify novel miRNAs candidates for their potential role as diagnostic, prognostics or therapeutic biomarkers in HNSCC patient-derived primary cells in the Pakistani population. miRNA species and their gene targets reported in HNSCC were identified using the miRbase, miRNet, and miRCancer databases, and a total of 69 miRNAs with differential expression levels in HNSCC were selected to seed a miRNA-Gene interaction network that was created using BioGrid and STRING data. Hub genes that were targeted by over-expressed miRNAs were predicted using miRTarbase. GO and KEGG analysis was carried out for the 181 interacting genes including TP53, SMAD4, PTEN, NOTCH2, and STAT3. Enrichment analysis demonstrated the increased involvement of these miRNAs in Cancer Pathways such as Hippo signaling Pathways and FoxO signaling pathways. We prioritized hub genes that were targeted by the highest number of tumor suppressor genes, and identified five miRNA species, including miR-21-5p, miR-16-5p, miR30a-5p, miR-93-5p, and miR106b-5p, as the best biomarker candidates for experimental validation. To validate the in silico findings, the top five microRNA candidates are being screened for expression in a library of local patient-derived primary cell lines from Pakistani HNSCC patients. Citation Format: Laiba Shah, Maryam Shah, Abdus Salam, Khudeja Salim, Faisal F. Khan. Identification and in vitro validation of miRNA biomarker candidates in head and neck squamous cell carcinoma using a network biology approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1485.