KHDRBS3 (KH RNA binding domain containing, signal transduction associated 3) is an RNA-binding protein that plays critical roles in cancer progression and therapeutic resistance across multiple tumor types. The protein functions as a post-transcriptional regulator, stabilizing target mRNAs and modulating cellular metabolism 1. KHDRBS3 promotes cell proliferation by causing G0/G1 phase arrest when silenced, indicating its essential role in cell cycle progression 2. The protein demonstrates oncogenic properties through distinct mechanisms in different cancer types: it enhances glycolysis and chemotherapy resistance in epithelial ovarian cancer via the MIR17HG/CLDN6 signaling axis 3, promotes hepatocellular carcinoma malignancy by upregulating 14-3-3ζ expression 4, and facilitates glioblastoma stem cell self-renewal and temozolomide resistance 5. In prostate cancer, KHDRBS2 and KHDRBS3 exhibit mutually exclusive expression patterns and regulate AR-V7 splice variant expression 6. KHDRBS3 is frequently amplified in medulloblastoma at chr8 region 8q24.22-q24.23, suggesting its role as a putative oncogene 7. The protein's involvement in drug resistance mechanisms makes it an attractive therapeutic target, with organoid studies identifying it as a key resistance mediator 8.