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Ref Type Journal Article
PMID (38408285)
Authors Mühlenberg T, Falkenhorst J, Schulz T, Fletcher BS, Teuber A, Krzeciesa D, Klooster I, Lundberg M, Wilson L, Lategahn J, von Mehren M, Grunewald S, Tüns AI, Wardelmann E, Sicklick JK, Brahmi M, Serrano C, Schildhaus HU, Sievers S, Treckmann J, Heinrich MC, Raut CP, Ou WB, Marino-Enriquez A, George S, Rauh D, Fletcher JA, Bauer S
Title KIT ATP-Binding Pocket/Activation Loop Mutations in GI Stromal Tumor: Emerging Mechanisms of Kinase Inhibitor Escape.
Journal Vol Issue Date Pages Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 42 12 2024 Apr 20 1439-1449 J Clin Oncol
URL
Abstract Text Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary KIT mutations, and clonal heterogeneity of these secondary mutations represents a major treatment obstacle. KIT inhibitors used after imatinib have clinical activity, albeit with limited benefit. Ripretinib is a potent inhibitor of secondary KIT mutations in the activation loop (AL). However, clinical benefit in fourth line remains limited and the molecular mechanisms of ripretinib resistance are largely unknown.Progressing lesions of 25 patients with GISTs refractory to ripretinib were sequenced for KIT resistance mutations. Resistant genotypes were validated and characterized using novel cell line models and in silico modeling.GISTs progressing on ripretinib were enriched for secondary mutations in the ATP-binding pocket (AP), which frequently occur in cis with preexisting AL mutations, resulting in highly resistant AP/AL genotypes. AP/AL mutations were rarely observed in a cohort of progressing GIST samples from the preripretinib era but represented 50% of secondary KIT mutations in patients with tumors resistant to ripretinib. In GIST cell lines harboring secondary KIT AL mutations, the sole genomic escape mechanisms during ripretinib drug selection were AP/AL mutations. Ripretinib and sunitinib synergize against mixed clones with secondary AP or AL mutants but do not suppress clones with AP/AL genotypes.Our findings underscore that KIT remains the central oncogenic driver even in late lines of GIST therapy. KIT-inhibitor combinations may suppress resistance because of secondary KIT mutations. However, the emergence of KIT AP/AL mutations after ripretinib treatment calls for new strategies in the development of next-generation KIT inhibitors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
KIT I748D missense unknown KIT I748D lies within the protein kinase domain of the Kit protein (UniProt.org). I748D is associated with resistance to KIT inhibitors (PMID: 38408285), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024). Y
KIT I798T missense unknown KIT I798T lies within the protein kinase domain of the Kit protein (UniProt.org). I798T has been identified in scientific literature (PMID: 38408285), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024).
KIT K558_V559delinsN indel gain of function - predicted KIT K558_V559delinsN results in a deletion of two amino acids in the juxtamembrane domain (exon 11) of the Kit protein from amino acids 558 to 559, combined with the insertion of an asparagine (N) at the same site (PMID: 16226710). K558_V559delinsN is associated with resistance to KIT inhibitors (PMID: 38408285) and has not been characterized, however similar Kit exon 11 deletions are activating (PMID: 9438854, PMID: 15365079), and therefore, is predicted to lead to a gain of Kit protein function. Y
KIT S645_L647dup duplication unknown KIT S645_L647dup (also referred to as L647_G648insSYL) indicates the insertion of three duplicate amino acids, serine (S)-645 through leucine (L)-647, in the protein kinase domain of the Kit protein (UniProt.org). S645_L647dup is associated with resistance to KIT inhibitors (PMID: 38408285), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024). Y
KIT T574_P577del deletion gain of function - predicted KIT T574_P577del (also referred to as P573_L576del) results in the deletion of four amino acids in the juxtamembrane domain (exon 11) of the Kit protein from amino acids 574 to 577 (PMID: 16226710). T574_P577del is associated with resistance to KIT inhibitors (PMID: 38408285) and has not been characterized, however similar Kit exon 11 deletions are activating (PMID: 9438854, PMID: 15365079), and therefore, is predicted to lead to a gain of Kit protein function. Y
KIT V654G missense unknown KIT V654G lies within the protein kinase domain of the Kit protein (UniProt.org). V654G is associated with resistance to KIT inhibitors (PMID: 38408285), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024). Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT exon 11 del KIT N822K gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT N822K in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT T670I gastrointestinal stromal tumor predicted - resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT T670I demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT A502_Y503dup gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup in culture (PMID: 38408285). 38408285
KIT A502_Y503dup gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line expressing KIT A502_Y503dup demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion in culture (PMID: 38408285). 38408285
KIT W557_K558del KIT V654A KIT D820V gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT W557_K558del progressed on fourth-line treatment with Qinlock (ripretinib) after 3.0 months and was found to have acquired KIT V654A and D820V in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT D820Y gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D820Y in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT A829P gastrointestinal stromal tumor resistant Ripretinib + Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and A829P demonstrated resistance to the combination of Qinlock (ripretinib) and Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A gastrointestinal stromal tumor decreased response Nintedanib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT V654A demonstrated reduced sensitivity to Ofev (nintedanib) compared to the parental cell line harboring a KIT exon 11 deletion in culture (PMID: 38408285). 38408285
KIT exon 11 del gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion in culture (PMID: 38408285). 38408285
KIT M552_E554delinsK KIT V654A gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT M552_E554delinsK progressed on second-line treatment with Qinlock (ripretinib) after 2.5 months and was found to have acquired KIT V654A in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT N822K gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT N822K and V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT A829P gastrointestinal stromal tumor sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT A829P and V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT A829P gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT A829P demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D820Y gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D820Y demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D820A gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D820A in culture (PMID: 38408285). 38408285
KIT N560_Y574del KIT V654A gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT N560_Y574del and N822Y progressed on second-line treatment with Qinlock (ripretinib) after 1.5 months and was found to have lost KIT N822Y but acquired KIT V654A in the metastatic lesion (PMID: 38408285). 38408285
KIT W557_K558del KIT V654A gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT W557_K558del progressed on second-line treatment with Qinlock (ripretinib) after 3 months and was found to have acquired KIT V654A in the metastatic lesion (PMID: 38408285). 38408285
KIT W557_K558del KIT V654G KIT D816H gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT W557_K558del and D816H progressed on sixth-line treatment with Qinlock (ripretinib) after 11.5 months and was found to have acquired KIT V654G in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT A829P gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT A829P in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT A829P gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT A829P and V654A in culture (PMID: 38408285). 38408285
KIT Q556_V559delinsH KIT T670I gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT Q556_V559delinsH progressed on third-line treatment with Qinlock (ripretinib) after 5.0 months and was found to have acquired KIT T670I in the metastatic lesion (PMID: 38408285). 38408285
KIT A502_Y503dup KIT N822K gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup and expressing KIT N822K demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT N822K gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and N822K demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D816A gastrointestinal stromal tumor resistant Ripretinib + Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and D816A demonstrated resistance to the combination of Qinlock (ripretinib) and Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT A502_Y503dup KIT T574_P577del KIT V654A KIT N822K gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT A502_Y503dup progressed on third-line treatment with Qinlock (ripretinib) after 7.0 months and was found to have acquired KIT T574_P577del (reported as P573_L576del), V654A, and N822K in one of the metastatic lesions (PMID: 38408285). 38408285
KIT K642E KIT N822Y gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT N822Y progressed on sixth-line treatment with Qinlock (ripretinib) after 7.3 months and was found to have acquired KIT K642E in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT D820Y gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT D820Y in culture (PMID: 38408285). 38408285
KIT P551_E554delinsQ KIT S645_L647dup KIT D820Y gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT P551_E554delinsQ and D820Y progressed on third-line treatment with Qinlock (ripretinib) after 29 months and was found to have acquired KIT S645_L647dup (reported as L647_G648insSYL) in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT A829P gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and A829P demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D820A gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT D820A and V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT Q556_V559delinsH KIT Y823D gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT Q556_V559delinsH and Y823D progressed on fourth-line treatment with Qinlock (ripretinib) after 22.1 months and was found to have acquired KIT Y646C in the metastatic lesion (PMID: 38408285). 38408285
KIT K550_K558del KIT V654A KIT A829P gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT K550_K558del and KIT A829P progressed on fifth-line treatment with Qinlock (ripretinib) after 8.0 months and was found to have acquired KIT V654A in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D820A gastrointestinal stromal tumor sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT D820A and V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT C809G gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT C809G in culture (PMID: 38408285). 38408285
KIT K558_V559delinsN KIT T670E gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, KIT K558_V559delinsN and T670E were identified in a post-progression biopsy of a patient with a gastrointestinal stromal tumor who had been on third-line treatment with Qinlock (ripretinib) for 5.1 months (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D820A gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT D820A and V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D816E gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D816E demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D816A gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D816A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D816A gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D816A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT T670I in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A gastrointestinal stromal tumor sensitive Ripretinib + Sunitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Qinlock (ripretinib) and Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A in culture (PMID: 38408285). 38408285
KIT Q556_K558delinsE KIT V654A KIT Y823H gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT Q556_K558delinsE and KIT V654A progressed on fourth-line treatment with Qinlock (ripretinib) after 8.5 months and was found to have acquired KIT Y823H in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT D820A gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT D820A in culture (PMID: 38408285). 38408285
KIT W557_K558del KIT V654A KIT I748D gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT W557_K558del and T670E progressed on fifth-line treatment with Qinlock (ripretinib) after 12 months and was found to have lost T670E but acquired KIT V654A and I748D in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT D820A gastrointestinal stromal tumor sensitive Ripretinib + Sunitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Qinlock (ripretinib) and Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D820A in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D820A gastrointestinal stromal tumor resistant Ripretinib + Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and D820A demonstrated resistance to the combination of Qinlock (ripretinib) and Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT T670I in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT A829P gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT A829P and V654A in culture (PMID: 38408285). 38408285
KIT A502_Y503dup KIT N822K gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup and expressing KIT N822K in culture (PMID: 38408285). 38408285
KIT V559_E561del KIT T670I gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT V559_E561del and KIT D820Y progressed on third-line treatment with Qinlock (ripretinib) after 2.5 months and was found to have lost KIT D820Y but acquired KIT T670I in the metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D816A gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and D816A demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT A502_Y503dup gastrointestinal stromal tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D816E gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D816E in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT D820A gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT V654A KIT D820A gastrointestinal stromal tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT V654A and D820A demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). 38408285
KIT exon 11 del KIT N822K gastrointestinal stromal tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and expressing KIT N822K demonstrated resistance to Sutent (sunitinib) in culture (PMID: 38408285). 38408285
KIT K550_V555del KIT V654A KIT C809G gastrointestinal stromal tumor predicted - resistant Ripretinib Case Reports/Case Series Actionable In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT K550_V555del progressed on sixth-line treatment with Qinlock (ripretinib) after 18 months and was found to have acquired KIT K550_V555del and V654A KIT C809G in one metastatic lesion and KIT V654A in a second metastatic lesion (PMID: 38408285). 38408285
KIT exon 11 del gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion in culture (PMID: 38408285). 38408285