Abstract 6890: 2D Tumor cell culture based Ex vivo drug sensitivity screening platform for South African patient samples (leukemia, multiple myeloma, ovarian and uterine cancer) demonstrate potential for targeted cancer therapies
Authors: Takundwa Mutsa , Kenmogne Vanelle , Malise Thudzelani , Monchusi Bernice , Dube Phumuzile , Nweke Ekene , Fabian June , Maher Heather , du Toit Justin , Philip-Cherian Vinitha , Fru Pascaline , Sajo Adekunle , Mouton Arnold (Arrie) , van Aardt Matthys C. , Visser Cathy , Dreyer Greta , Govindaraj Deepak 
Published: March 2024

Resistance to standard chemotherapy is a major challenge with Leukemia (Leuk), Multiple Myeloma (MM), Ovarian Cancer (OvCa) and Uterine Cancer (UtCa) treatments, which ultimately leads to relapse. Our study objective is to establish a robust drug sensitivity screening platform that can identify drugs and drug combinations that are effective in precision medicine for individual South African patient samples (Leuk, MM, OvCa and UtCa). Given that resistance to chemotherapy treatment accounts for high mortality and morbidity, we focus on the hypothesis that several drug combinations will be required for patients to achieve better response for drug regimens beyond first line of chemotherapy. Therefore, our defined objectives were to 1) establish 2D ex vivo tumour cell culturing using South African patient samples; 2) develop a drug sensitivity screening platform through which selected single and drug combinations will be identified; 3) to provide South African cancer (OvCa, Ut Ca, CLL, MM) patients with individualized treatment options with effective drug combinations for targeted therapies. Through collaboration with, Steve Biko Hospital Pretoria, Chris Hani Baragwanath Hospital and Wits Donald Gordon Medical Centre, Johannesburg, South Africa, we performed 100 patient sample collections including Acute myeloid leukaemia (AML) (n=7), Chronic lymphocytic leukaemia (CLL) (n=4), Chronic myeloid leukaemia (CML) (n= 30), MM (n=40), OvCa (n=10), UtCa (n=4) and healthy donors (n=5). Culture setting for all patient-derived tumor cells were established through the 2D cancer cell culturing in 96 well plates. This was followed by functional drug sensitivity testing using a panel of FDA approved chemotherapy drugs. The average turnaround time from biopsy to drug sensitivity test results is currently at 14 days. We have completed ex vivo drug sensitivity screening to perform analysis on patient samples (n=80) using 30 drugs with a concentration range of 1-1000 nm. Our preliminary drug sensitivity screening studies show good response to proteosome inhibitors, melphalan, doxorubicin and kinase inhibitors. We have established a wound healing assay for OvCa and UtCa samples and demonstrated sustained cell growth for the period of 2 weeks with tumor cells growing faster than twin normal tissue. We are now at stage of performing drug sensitivity screening for OvCa and UtCa patient samples for both twin normal and tumor tissues. We have established a drug sensitivity screening platform and wound healing assay with primary patient derived cells that utilizes South African Patient samples to select effective drugs for monotherapy and also drug combinations.

Citation Format: Mutsa Takundwa, Vanelle Kenmogne, Thudzelani Malise, Bernice Monchusi, Phumuzile Dube, Ekene Nweke, June Fabian, Heather Maher, Justin du Toit, Vinitha Philip-Cherian, Pascaline Fru, Adekunle Sajo, Arnold (Arrie) Mouton, Matthys C. van Aardt, Cathy Visser, Greta Dreyer, Deepak Govindaraj. 2D Tumor cell culture based Ex vivo drug sensitivity screening platform for South African patient samples (leukemia, multiple myeloma, ovarian and uterine cancer) demonstrate potential for targeted cancer therapies [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 6890.