Multi-omic approaches to improve outcome for T-cell acute lymphoblastic leukemia patients
| Autor: | Jordy C.G. van der Zwet, Jules P.P. Meijerink, Valentina Cordo, Kirsten Canté-Barrett |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research medicine.medical_treatment T cell Genomics Disease Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Bioinformatics Transcriptome 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor Genetics medicine Humans Child Molecular Biology Chemotherapy business.industry Omics medicine.disease Leukemia 030104 developmental biology medicine.anatomical_structure Drug Resistance Neoplasm Child Preschool 030220 oncology & carcinogenesis Mutation Molecular Medicine Female Personalized medicine business |
| Zdroj: | Advances in Biological Regulation. 74:100647 |
| ISSN: | 2212-4926 |
| Popis: | In the last decade, tremendous progress in curative treatment has been made for T-ALL patients using high-intensive, risk-adapted multi-agent chemotherapy. Further treatment intensification to improve the cure rate is not feasible as it will increase the number of toxic deaths. Hence, about 20% of pediatric patients relapse and often die due to acquired therapy resistance. Personalized medicine is of utmost importance to further increase cure rates and is achieved by targeting specific initiation, maintenance or resistance mechanisms of the disease. Genomic sequencing has revealed mutations that characterize genetic subtypes of many cancers including T-ALL. However, leukemia may have various activated pathways that are not accompanied by the presence of mutations. Therefore, screening for mutations alone is not sufficient to identify all molecular targets and leukemic dependencies for therapeutic inhibition. We review the extent of the driving type A and the secondary type B genomic mutations in pediatric T-ALL that may be targeted by specific inhibitors. Additionally, we review the need for additional screening methods on the transcriptional and protein levels. An integrated 'multi-omic' screening will identify potential targets and biomarkers to establish significant progress in future individualized treatment of T-ALL patients. |
| Databáze: | OpenAIRE |
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