Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumors: Small Steps Toward Personalized Medicine?
Gloria RavegniniRiccardo RicciPublished in: Epigenetics insights (2019)
Various molecular triggers define heterogeneous subsets of gastrointestinal stromal tumors (GISTs), differing in clinical behavior and drug sensitivity. KIT/PDGFRA-wild-type GISTs, including those succinate dehydrogenase (SDH)-deficient, are overall unresponsive to the tyrosine kinase inhibitors commonly used, fostering the development of specific alternative therapeutic strategies. Epigenetic inactivation of O6-methylguanine-DNA methyltransferase (MGMT) through promoter methylation leads to effectiveness of alkylating agents in several human cancers. SDH-deficient GISTs typically feature widespread DNA methylation. However, the actual occurrence of MGMT methylation in these tumors, potentially predisposing them to respond to alkylating drugs, has not been investigated so far. Here we discuss the recent findings concerning the occurrence of MGMT methylation in different GIST subgroups, including SDH-deficient ones, as a premise for a possible reappraisal of alkylating agents specifically targeting these small, otherwise overall chemorefractory, GIST subgroups.
Keyphrases
- dna methylation
- wild type
- genome wide
- gene expression
- risk assessment
- endothelial cells
- randomized controlled trial
- systematic review
- single molecule
- machine learning
- copy number
- deep learning
- emergency department
- peripheral blood
- circulating tumor
- cancer therapy
- drug delivery
- young adults
- transcription factor
- induced pluripotent stem cells
- drug induced
- high resolution
- neural network
- adverse drug