Colorectal cancer is a leading cause of cancer deaths. Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies. Here, we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment. Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression. CRISPR/Cas9 silencing of fibroblast growth factor receptor 1 (FGFR1) and oxytocin receptor (OXTR) helped overcome oxaliplatin resistance. Similarly, treatment with oxaliplatin in combination with an FGFR1 inhibitor (PD166866) or an antagonist of OXTR (L-368,899) suppressed chemoresistant organoids. However, oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid, suggesting that chromatin accessibility changes are patient-specific. The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

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Background: Acute tubulointerstitial nephritis (ATIN) is a very rare paraneoplastic manifestation in patients with multiple myeloma (MM). It is an uncommon pattern of renal disease in such patients. Case presentation: We report a case of an 82-year-old male who was admitted with acute kidney injury. Renal biopsy showed typical findings of light chainassociated ATIN with scattered inflammatory cells in the interstitium and associated active tubulitis. No other common manifestations of MM were present at the time of presentation, including hypercalcemia, hyperuricemia, proteinuria, bone pain or lytic bone lesions. Subsequent immunoassays revealed significant serum lambda light chain burden and Bence Jones protein in urine. Immunofluorescence demonstrated linear tubular basement membranes with positive staining for lambda light chain (3+). Electron microscopy (EM) further showed interstitial edema and inflammation. All the aforementioned findings are consistent with ATIN and supported the diagnosis of MM. Conclusions: In conclusion, light chain-associated ATIN should be considered in the differential diagnosis of acute interstitial nephritis. Henceforth, serum free light chains as well as serum and urine protein electrophoresis should be included in the workup of such patients.