KIT W557

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P2, N=40, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Our findings show that piRNA-MW557525 functions as a tumor suppressor gene in NB and may serve as an innovative biomarker and possible therapeutic target for NB.

We found that farnesyltransferase inhibitors tipifarnib and lonafarnib, which inhibit RAS activity, inhibited ERK activation mediated by both wild-type and KIT mutants, which often occur in gastrointestinal stromal tumors. Similar to the primary KIT mutations, secondary mutations of KIT-induced ERK activation and cell response were inhibited by both inhibitors. Our results suggested the potential benefit of farnesyltransferase inhibitors either alone or combined with imatinib in the treatment of gastrointestinal stromal tumors carrying KIT mutations.

P2, N=40, Recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2023 --> Dec 2023

P2, N=40, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

IDRX-42 showed significant antitumor activity in patient- and cell line-derived GIST xenograft models. The novel kinase inhibitor induced volumetric responses, decreased mitotic activity and had antiproliferative effects. In models with KIT exon 13 mutation IDRX-42 induced characteristic myxoid degeneration.

P2, N=40, Recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2023 --> Sep 2023

P2, N=40, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Dec 2022 --> Jun 2023

All 3 patients underwent surgery and imatinib therapy...Summarizing the reported kindreds, the majority of familial GISTs manifest as multiple primary GISTs complicated with special clinical manifestations, including cutaneous hyperpigmentation, dysphagia, mastocytosis, inflammatory fibrous polyps, and large hands. Familial GISTs are generally thought to exhibit TKI sensitivity similar to that of sporadic GISTs with the same mutation.

The best outcome was achieved using imatinib in a patient with a KIT mutation (p.W557R)...The patient was still on ponatinib when the observation period ended. We demonstrate that comprehensive molecular analysis provides clinically relevant information in a subgroup of TET patients... We demonstrate that comprehensive molecular analysis provides clinically relevant information in a subgroup of TET patients. Thymoma, TCs, and NETs present with different molecular characteristics. Distinction between immunologically hot and cold TCs may have value for risk stratification and therapeutic strategies.

However dedifferentiation with altered morphology and loss of CD117 and DOG1 expression can make the diagnosis difficult. Molecular tests resolve the problem by detecting genetic abnormalities usually described in GISTs.

Mice were treated daily with vehicle (control), imatinib (100mg/kg), avapritinib (5mg/kg), sunitinib (20mg/kg), or M4205 (10mg/kg, 25mg/kg). Conclusions M4205 has significant antitumor activity in patient- and cell line-derived GIST xenograft models. The novel kinase inhibitor induces volumetric responses, decreases mitotic activity, has antiproliferative effects and in models with KIT exon 13 mutation leads to characteristic myxoid degeneration.

Background: The majority of GISTs are driven by constitutively activated KIT/PDGFRA kinases and susceptible to treatment with tyrosine kinase inhibitors such as imatinib, sunitinib and regorafenib...Mice were treated daily with vehicle (control), imatinib (100mg/kg), avapritinib (5mg/kg), sunitinib (20mg/kg), or M4205 (10mg/kg, 25mg/kg)... M4205 has significant antitumor activity in patient- and cell line-derived GIST xenograft models. The novel kinase inhibitor induces volumetric responses, decreases mitotic activity, has antiproliferative effects and in models with KIT exon 13 mutation leads to characteristic myxoid degeneration. * Cornillie et al.