A5056728145- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Platelet Disorders and Treatments
- Gastric Cancer Management and Outcomes
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
Merck (Germany)
2021-2023
Abstract Primary activating mutations in KIT (exons 9/11) are key driver alterations about 80% of gastrointestinal stromal tumors (GIST). Imatinib, a small molecule tyrosine kinase inhibitor, is used successfully as first-line therapy for unresectable metastatic or recurrent GIST patients, but secondary resistance the domains frequently occur. Currently approved later-line therapies target these incompletely with limited clinical benefit. M4205, kinome-selective was designed to address this...
The treatment of gastrointestinal stromal tumors (GISTs) driven by activating mutations in the KIT gene is a prime example targeted therapy for cancer. approval tyrosine kinase inhibitor imatinib has significantly improved patient survival, but emerging resistance under and relapse observed. Several additional inhibitors have been approved; still, there high unmet need with selectivity broad coverage all clinically relevant mutants. An imidazopyridine hit featuring excellent was identified...
Abstract Therapeutic strategies based on exacerbated stress signaling may represent novel and effective treatment paradigms in oncology. Here, we disclose for the first time endoplasmic reticulum (ER) modulator (ERSM) M3913 that was discovered developed following a phenotypic screening campaign. Mechanistically, engages an ER transmembrane protein not yet implicated cancer biology to induce Ca2+ shift from towards cytoplasm, resulting unfolded response subsequent antitumor activity sensitive...
Abstract Oncogenic mutations in cKIT exons 9 and 11 are the main driver of gastrointestinal stromal tumors (GIST). Imatinib is standard care 1L unresectable metastatic or recurrent GIST, yet secondary resistance 13/14 17/18 kinase domain frequently arise limiting efficacy. Currently approved 2L 3L therapies sunitinib regorafenib target these only to some extent show limited clinical benefit. Even with recent approval ripretinib as 4L treatment, a high unmet medical need remains for patients...