TY - CHAP
T1 - Molecular pathobiology of gastrointestinal stromal sarcomas
AU - Corless, Christopher L.
AU - Heinrich, Michael C.
PY - 2008
Y1 - 2008
N2 - Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas whose unique pathobiology provides a model of how molecularly targeted therapeutics can have a major impact on patient welfare. Approximately 85% of GISTs are driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT or platelet-derived growth factor receptor α. We review the pivotal relationship between specific mutations in these kinase genes, the origin and pathologic spectrum of GISTs, and the response of these tumors to treatment with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance to kinase inhibitor therapy are discussed, and targets for the next generation of therapeutics are considered. The rapid evolution in our understanding of GISTs, which stems directly from the close alliance of basic and clinical researchers in the field, illustrates the growing role of the molecular classification of solid tumors in the development of modern oncological treatments.
AB - Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas whose unique pathobiology provides a model of how molecularly targeted therapeutics can have a major impact on patient welfare. Approximately 85% of GISTs are driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT or platelet-derived growth factor receptor α. We review the pivotal relationship between specific mutations in these kinase genes, the origin and pathologic spectrum of GISTs, and the response of these tumors to treatment with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance to kinase inhibitor therapy are discussed, and targets for the next generation of therapeutics are considered. The rapid evolution in our understanding of GISTs, which stems directly from the close alliance of basic and clinical researchers in the field, illustrates the growing role of the molecular classification of solid tumors in the development of modern oncological treatments.
KW - Gist
KW - Imatinib
KW - Sunitinib
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=41749118496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41749118496&partnerID=8YFLogxK
U2 - 10.1146/annurev.pathmechdis.3.121806.151538
DO - 10.1146/annurev.pathmechdis.3.121806.151538
M3 - Chapter
C2 - 18039140
AN - SCOPUS:41749118496
SN - 9780824343033
T3 - Annual Review of Pathology: Mechanisms of Disease
SP - 557
EP - 586
BT - Annual Review of Pathology
ER -