C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

OBJECTIVES: STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). METHODS: PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. RESULTS: C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. CONCLUSIONS: In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

BME-free primary patient-specific organoids obtained with a one-day mimicking method to replicate the corresponding tumor for personalized treatment options.

Introduction: In cancer treatment, every minute counts. Due to the unpredictable behavior of cancer cells caused by continuous mutations, each cancer patient has a unique situation and may or may not respond to a specific drug or treatment. The process of finding an effective therapy can be time-consuming, but cancer patients do not have the luxury of time for trial and error. Therefore, a novel technology to fast generate a patient relevant organoid for the therapies selecting is urgently needed. Methods: Utilizing the new organoid technology by specially dissolving the mesenchyme in tumor tissues acquired from cancer patients, we realized the work of creating patient-specific organoids (PSO) within one day. Results: PSO properties reflect those of its respective original in vivo tumor tissue and can be utilized to perform various in vitro drug sensitivity tests to identify the most effective clinical treatment for patients. Additionally, PSO can aid in assessing the efficacy of immune cell therapies. Discussion: Organoid technology has advanced significantly in recent years. However, current cancer organoid methods involve creating 3D tumor tissue from 2D cancer cells or cell clusters, primarily for cancer research purposes aimed at investigating related molecular and cellular mechanisms of tumor development. These methods are research-driven, not tailored towards clinical applications, and cannot provide personalized information for individual patients. PSO filled the gap of clinic-driven and time-saving method for the personalized therapies selecting to the cancer patients.