Patient-derived organoids for precision oncology: a platform to facilitate clinical decision making.

BACKGROUND: Despite recent advances in research, there are still critical lacunae in our basic understanding of the cause, pathogenesis, and natural history of many cancers, especially heterogeneity in patient response to drugs and mediators in the transition from malignant to invasive phenotypes. The explication of the pathogenesis of cancer has been constrained by limited access to patient samples, tumor heterogeneity and lack of reliable biological models. Amelioration in cancer treatment depends on further understanding of the etiologic, genetic, biological, and clinical heterogeneity of tumor microenvironment. Patient-derived organoids recapitulate the basic features of primary tumors, including histological complexity and genetic heterogeneity, which is instrumental in predicting patient response to drugs. METHODS: Human iPSCs from healthy donors, breast and ovarian cancer patients were successfully differentiated towards isogenic hepatic, cardiac, neural and endothelial lineages. Multicellular organoids were established using Primary cells isolated from tumor tissues, histologically normal tissues adjacent to the tumors (NATs) and adipose tissues (source of Mesenchymal Stem Cells) from ovarian and breast cancer patients. Further these organoids were propagated and used for drug resistance/sensitivity studies. RESULTS: Ovarian and breast cancer patients' organoids showed heterogeneity in drug resistance and sensitivity. iPSCs-derived cardiomyocytes, hepatocytes and neurons showed donor-to-donor variability of chemotherapeutic drug sensitivity in ovarian cancer patients, breast cancer patients and healthy donors. CONCLUSION: We report development of a novel integrated platform to facilitate clinical decision-making using the patient's primary cells, iPSCs and derivatives, to clinically relevant models for oncology research.

Derivation of Breast Cancer Patient Derived Human Induced Pluripotent Stem Cell Line (YBLi006-A) with FANC-BRCA Gene Mutations: A Resource for Precision & Personalized Medicine.

Fanconi anemia complementation group I (FANCI) is located on the chromosome 15q26.1 locus and becomes ubiquitinated following DNA damage. 3.06% of patients with breast cancer have altered FANCI gene. We generated an iPSC line (YBLi006-A) from peripheral blood mononuclear cells (PBMCs) of a patient carrying a mutation in FANCIgene (NM_001376911.1, NM_001376910.1, NM_001113378.2; c.80G > T, c.257C > T, c.2225G > C; p.Gly27Val, p.Ala86Val, p.Cys742Ser) using non-integrating Sendai virus technology. This unique breast cancer patient-derived-iPSC line will be resourceful to analyze the entire coding sequence and splicing sites ofFANCIin high-risk familial breast cancer.