The principle of imatinib/Gleevec in the treatment of GIST

Gastrointestinal stromal tumor (GIST) is a type of rare tumor derived from Cajal interstitial cells in the wall of the digestive tract. These cells are the "pacemakers" of gastrointestinal motility under normal circumstances. Most GIST patients have activating mutations in the KIT or PDGFRA genes. These mutations cause the corresponding tyrosine kinases to be continuously activated. Even in the absence of external signal stimulation, tumor cells can still obtain continuous proliferation and survival signals and thus continue to expand.

Imatinib/Gleevec (Imatinib) is a highly selective tyrosine kinase inhibitor that can compete with the ATP binding site of KIT or PDGFRA protein. It inhibits the division of tumor cells and promotes apoptosis of some cells by blocking kinase activity and cutting off downstream signaling pathways such as MAPK and PI3K/AKT. Unlike traditional chemotherapy, imatinib hardly affects the function of normal cells, so it is relatively well tolerated and long-term use can maintain disease stability.

In clinical practice, imatinib has become the standard first-line drug for advanced, unresectable or metastaticGIST, which can significantly delay tumor progression. In postoperative adjuvant therapy, for patients with a high risk of recurrence (such as large tumor diameter, high division rate or rupture), long-term use of imatinib can effectively reduce the recurrence rate and prolong disease-free survival.

It should be noted that not allGIST patients can benefit from imatinib. For example, PDGFRA D842V mutant GIST responds extremely poorly to imatinib, so international guidelines recommend that KIT and PDGFRA gene testing must be performed before starting treatment. Accurate detection can not only improve the pertinence of medication, but also avoid the time and economic losses caused by ineffective treatment.

Overseas and domestic real-world studies have shown that some GIST patients still maintain stable disease after taking imatinib for many years, demonstrating the important role of this drug in long-term disease control. But at the same time, the problem of drug resistance still exists, especially the occurrence of secondary mutations, and treatment strategies need to be adjusted according to the drug resistance mechanism.

Reference materials:https://www.gleevec.com/