HRAS G12V

Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Since RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects.

Mice with dedifferentiated tumors treated with 4 weeks of either lenvatinib or dabrafenib/trametinib (dab/tram) for Braf/Arid1a or tipifarnib for Hras/p53 demonstrated tumor progression or stability (% change tumor volume: Braf/Arid1a: vehicle +238. Combination MAPK signaling blockade and angiogenesis inhibition leads to profound anti‐tumor responses across the spectrum of thyroid cancers in GEMMs.

Low-dose rapamycin might be effective to prevent HCC growth, but may be ineffective as a treatment option after HCC development.

Experimental anti-tumour Benzoprims, analogues of the anti-malarial drug pyrimethamine, possess anti-tumour activity against metastatic melanoma cells, mainly by inhibiting dihydrofolate reductase (DHFR), a validated target in cancer therapy...Conclusion Benzoprims are most potent in CRC cell lines possessing mutant KRAS G13D . Although their mechanism of action independent of DHFR inhibition is still unclear, downregulation of proteins by SM1235 in HCT116 cells indicate that benzoprims inhibit proteins downstream of RAS.

Finally, RBM10 re-expression in RBM10 null cells reversed metastatic competency in vivo. In conclusion, RBM10 loss alters the ratio of cassette exon inclusion events in a subset of transcripts that regulate interactions between the ECM and the cytoskeleton, leading to RHO/RAC activation and governing a process favoring increased cell movement and metastatic competence.

Ras signaling was essential for the tyrosine phosphorylation of MerTK, and the kinase activity of MerTK was indispensable for accelerating cell migration. Collectively, the present results reveal a novel role for MerTK in cancer malignancy, which may be utilized to develop novel therapeutic strategies that target Ras-transformed cells.

Our studies provide a high resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers, which also reveal potentially targetable signaling networks uniquely deregulated in these cells. BRCA2 mutations are associated with distinct susceptibility to PIK3CA mutation-driven transformation. Since PIK3CA mutations are observed in clinically normal breast tissues, screening for such mutations in BRCA2 mutation carriers may help to detect pre-neoplastic or early stage breast cancer.

Combining cytology with ddPCR analysis of TERT, BRAF and RAS mutations can improve the diagnostic accuracy of thyroid FNABs.

Our results obtained in an engineered mouse model of hepatocarcinogenesis demonstrate a metabolic switch from OXPHOS to glycolysis caused by the concomitant overexpression of c-Myc and h-Ras, two of the most frequently altered oncogenes in HCC. This finding further supports the notion that targeting metabolism may represent a critical strategy for HCC therapy. Our studywill be further extended to a set of clinically relevant oncogenic cooperation to quickly unravel oncogene-specific metabolic vulnerabilities in HCC.

In this study, we have unveiled that the stem cell-immune cell crosstalk actually dictates the outcomes of successful tissue regeneration or tumor growth. These discoveries will provide a new revenue to leverage and target these vital crosstalk as novel cancer immunotherapy.

These findings demonstrate that genetic risk of RMS results from germline predisposition variants associated with a wide spectrum of cancer-susceptibility syndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.

HrasG12V-expressing BEC-E6E7/myc significantly increased MAPK/ERK signaling, whereas PI3K/AKT signaling was significantly elevated in KrasG12V-expressing SAEC-E6E7/myc. These results suggest a context dependency with oncogenic Ras mutations in tumorigenesis between lung adenocarcinoma and squamous cell carcinoma.

Mechanistically, LL22NC03-N14H11.1 recruited Myb proto-oncogene (c-Myb) to repress the transcription of leucine zipper-like transcription regulator 1 (LZTR1), so as to inhibit LZTR1-mediated ubiquitination of H-RAS (G12V), leading to the activation of mitogen-activated protein kinase (MAPK) signaling and induction of p-DRP1 (Serine 616). In conclusion, this study firstly revealed that lncRNA LL22NC03-N14H11.1 promoted HCC progression through activating H-RAS/MAPK pathway to induce mitochondrial fission, indicating LL22NC03-N14H11.1 as a novel potential biomarker for HCC treatment.