The activity of the resulting ADC, LOP628, was evaluated <i>in vitro</i> against GIST, SCLC, and AML models and <i>in vivo</i> against GIST and SCLC models.<b>Results:</b> LOP628 exhibited potent antiproliferative activity on c-KIT-positive cell lines, whereas LMJ729 displayed little to no effect.
Autocrine activation of c-kit (KIT receptor tyrosine kinase) has been postulated to be a potent oncogenic driver in small cell lung cancer, neuroblastoma (NB), and poorly differentiated colorectal carcinoma (CRC).
The finding revealed that stages was identified as an independent predictive factor for SCLC patients.Our finding reveals that somatic mutation of KIT is rare in SCLC patients from the northeast China and there is no enough evidence comfirming KIT inhibitors for treatment in SCLC.
Immunohistochemical studies of various antigens and genetic studies of KIT and platelet-derived growth factor-α (PDGFRA) have not been performed in gastric SCC.
The author investigated protein expression of KIT and PDGFRA in 54 Japanese cases of small cell lung carcinoma by immunohistochemistry, and gene mutations of KIT and PDGFRA in 20 Japanese cases of small cell lung carcinoma by the PCR-direct sequencing method.
The present case is the first of small cell carcinoma of the maxillary sinus with a comprehensive immunohistochemical examination and a gene analysis of KIT and PDGFRA.
The present case is the first reported case of primary small cell carcinoma of the pleura with an examination of KIT and PDGFRA expressions and KIT and PDGFRA gene mutations.
The present case is the first reported case of primary small cell carcinoma of the endometrium with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.
The present case is the first reported case of primary small cell carcinoma of the mediastinum with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.
The present case is the first case of primary small cell carcinoma of the urinary bladder involving examination of KIT and PDGFRA expression and KIT and PDGFRA gene mutations.
The level of c-kit mRNA expression was variable in SCLC tumors (positive for 2 of 4 xenografts), and c-kit protein was not detected by immunohistochemistry.
KIT tyrosine kinase inhibitors such as imatinib mesylate are the generally accepted treatment of metastatic GISTs, and their availability has prompted an active search for other treatment targets among KIT-positive tumors such as myeloid leukemias and small cell carcinoma of the lung, with variable and often nonconvincing results.
Patients with progressive SCLC after one or two previous chemotherapy regimens consented to have their tumor specimens screened by immunoperoxidase stain (CD117, Dako Corporation, Carpinteria, CA) for c-kit protein expression.
The level of c-kit mRNA expression was variable in SCLC tumors (positive for 2 of 4 xenografts), and c-kit protein was not detected by immunohistochemistry.
KIT immunostaining was rarely positive except in GISTs (18 of 18), small-cell lung cancer (10 of 30; 33%), and testicular teratocarcinoma (four of 17; 24%).
The KIT molecular profile derived from the analysis of SCLC surgical specimens shows that wild-type KIT is overexpressed and phosphorylated in the presence of stem cell factor.
The KIT molecular profile derived from the analysis of SCLC surgical specimens shows that wild-type KIT is overexpressed and phosphorylated in the presence of stem cell factor.
The recent observations that c-kit protooncogene, a tyrosine kinase, is overexpressed in a subset of small cell lung cancer and that selective kinase inhibitors block the in vitro growth of small cell lung cancer cell lines prompted us to investigate the expression and mutation status of the c-kit gene in colorectal neuroendocrine carcinomas.
Additionally, KIT inhibitors may play an adjunctive role in diseases such as small-cell lung cancer, in which KIT activation is secondary to ligand binding rather than an acquired mutation.
Taken together, these studies demonstrate that the coexpression of the stem cell factor and c-kit genes is a major contributor to the growth factor independence of SCLC.