Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions.
Liver kinase B1 (LKB1/STK11) is one of the most mutated genes in non-small-cell lung cancer (NSCLC) accounting for about one third of cases and its activity is impaired in about half of KRAS mutated NSCLC.
To explore the therapeutic potential of direct PP2A activation in a diverse set of MYC-driven cancers, here we used biochemical assays, recombinant cell lines, gene expression analyses, and immunohistochemistry to evaluate a series of first-in-class small-molecule activators of PP2A (SMAPs) in Burkitt lymphoma, KRAS-driven non-small cell lung cancer, and triple-negative breast cancer.
Patients with previously treated advanced KRAS mutant NSCLC were prospectively assigned to one of four molecularly defined cohorts based on the presence or absence of TP53 or CDKN2A alterations and received treatment with defactinib 400 mg orally BID until disease progression or intolerable toxicity.
The present study explored the association between <i>KRAS proto-oncogene GTPase (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and tumor protein p53 (TP53) mutations, and the clinical features and survival prognosis in 50 patients with non-small cell lung cancer (NSCLC).
Here, we demonstrate that CD4<sup>+</sup> T cells when incubated with tumor-derived exosomes from mutant (MT) KRASnon-small-cell lung cancer (NSCLC) cells, patient sera, or a mouse xenograft model, induce phenotypic conversion to FOXP3<sup>+</sup> Treg-like cells that are immune-suppressive.
NKT can activate AMP-activated protein kinase (AMPK) in liver and muscle cells, however, little is known about the role of NKT in cancer, particularly its role in NSCLC with high rates of liver kinase B1 (LKB1) and KRAS mutations.
No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC.
Therefore, combination strategies are likely needed to improve efficacy.<b>Experimental Design:</b> To identify strategies to maximally leverage direct KRAS inhibition we defined the response of a panel of NSCLC models bearing the KRASG12C-activating mutation <i>in vitro</i> and <i>in vivo</i>.
The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non-small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFR T790M in non-small-cell lung cancer. ctDNA can also detect mutations such as KRASG12V in colorectal cancer and BRAF V600E/V600K in melanoma.
Transformation to small cell lung cancer and activation of KRAS during long-term erlotinib maintenance in a patient with non-small cell lung cancer: A case report.
Here we show that genetic inhibition of SHOC2 suppresses tumorigenic growth in a subset of KRAS-mutant NSCLC cell lines and prominently inhibits tumour development in autochthonous murine KRAS-driven lung cancer models.
Here, we found that the stemness of KRAS-mutant NSCLC cells but not the KRAS-wild type NSCLC cells was promoted by TKIs treatment, as evident by the increase of ALDH1 activity, stemness marker expression and spheroid formation ability.
The combination of BTK-TKIs with EGFR-TKIs is cytotoxic for EGFR-wt/KRAS-mutant/p53-null tumors and BTK-TKIs re-sensitizes drug-resistant NSCLC to SOC chemotherapy.
It can meet the demands of the clinical detection on the KRAS point mutation level in blood samples, which means significant for the earlier NSCLC diagnosis, individualized treatment, and therapeutic efficacy evaluation.