Acquired resistance to targeted inhibitors remains a major, and inevitable, obstacle in the treatment of oncogene-addicted cancers. Newer-generation inhibitors may help overcome resistance mutations, and inhibitor combinations can target parallel pathways, but durable benefit to patients remains elusive in most clinical scenarios. Now, recent studies suggest a third approach may be available in...

The TRK-T1 oncogene, isolated from a human thyroid carcinoma, represents a rearranged form of the high affinity nerve growth factor (NGF) receptor encoded by the NTRK1 gene; it is created by an intrachromosomal rearrangement fusing the NTRK1 tyrosine kinase domain to the 5' portion of the TPR gene. We have investigated the effect of the TRK-T1 oncogene in PC12 cells, a model system for studying...

Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF1...

Download ammalian cells, activation of oncogenes usually triggers innate tumor-suppressing defense mechanisms, ing apoptosis and senescence, which are compromised by additional mutations before cancers are develThe miR-17-92 gene cluster, a polycistron encoding six microRNAs (miRNA), is frequently overexpressed an cancers and has been shown to promote several aspects of oncogenic transformation...

The main modifications that characterize cancer are represented by alterations in onco‐ genes, tumor-suppressor genes, and non-coding RNA genes. Most of these alterations are somatic and the process is a multistep one. Tumors often arise from an initial trans‐ formed cell, and after subsequent genetic alterations different cytogenetically clones lead to tumor heterogeneity. Oncogenes encode pro...

p21 is a cyclin-dependent kinase (cdk) inhibitor, and is a key mediator of p53-dependent cell cycle arrest after DNA damage (1, 2). p21 belongs to the Cip/Kip family of cdk inhibitors and it inhibits proliferation mainly by interfering with cyclin E/cdk2 activity (3). The initial perception of p21 functions was that it might be a tumor suppressor because it inhibits proliferation, and subsequen...

The Sloan-Kettering viruses (SKVs) are a group of transforming retroviruses that were isolated from chicken embryo cells which had been infected with the avian leukosis virus transformation-defective Bratislava 77 (tdB77). Each of the SKV isolates was shown to contain multiple genomes of different sizes indicating the presence of several viruses in addition to tdB77. To identify and characteriz...

Hereditary medullary thyroid carcinoma (MTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. Associations between specific RET mutations (genotype) and the aggressiveness of MTC and presence or absence of other endocrine neoplasms (phenotype) are well documented. Mutations in six exons (10, 11, 13, 14, 15, and 16) located in either cysteine-rich or tyrosine...

Oncogene inactivation in both clinical targeted therapies and conditional transgenic mouse cancer models can induce significant tumor regression associated with the robust induction of apoptosis. Here we report that in MYC-, RAS-, and BCR-ABL-induced acute lymphoblastic leukemia (ALL), apoptosis upon oncogene inactivation is mediated by the same pro-apoptotic protein, BIM. The induction of BIMi...

AIM To evaluate the relationship between vascular endothelial growth factor (VEGF), p53, and the H-ras oncogene and different clinicopathological parameters in Egyptian patients with Schistosoma-associated transitional cell carcinoma of the bladder. METHODS The study included 50 patients with transitional cell carcinoma for whom radical cystectomy and urinary diversions were carried out. VEGF...