ABSTRACT
BACKGROUND: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. METHODS: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. RESULTS: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. CONCLUSION: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. TRANSLATIONAL POTENTIAL STATEMENT: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.
ABSTRACT
With the rapid development of omics and big data technology, there have been multiple achievements with the use of pre-cision medicine for cancer treatment. Osteosarcoma, the most common primary malignant tumor of the skeletal system, primarily oc-curs in children and adolescents. Since the 1970s, surgical resection and chemotherapy have been the main treatments for osteosarco-ma; however, the survival rate for this type of cancer has been stagnant due to high genetic heterogeneity. Precision medicine can pro-vide a precise diagnosis and tailored treatments based on the patients’biological characteristics using techniques such as omics. Therefore, application of precision medicine is promising for studying osteosarcoma and improving patient survival rates. This study aims to systematically review the progress of precision medicine in advancing osteosarcoma treatment. In addition, it discusses the prospects and future direction of osteosarcoma precision treatment.
