Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Squamous cell carcinoma of the head and neck (HNSCC) is the eighth most common disease, affecting approximately 640,000 patients worldwide each year. Despite recent advances in surgery, radiotherapy, and chemotherapy, the overall cure for patients with HNSCC has remained at less than 50% for many decades. Patients with recurrent and metastatic disease have a median survival of only 6-10 months. Systemic chemotherapy is the only treatment option for those patients. New treatment options are thus desperately needed to supplement, complement, or replace currently available therapies. New agents that target molecular and cellular pathways of the disease pathogenesis of HNSCC are promising candidates. One class of these new agents is angiogenesis inhibitors that have been proven effective in the treatment of advanced colorectal, breast, and non-small cell lung cancers. Similar to other solid tumors, angiogenesis plays an important role in the pathogenesis of HNSCC. A number of angiogenic factors including vascular endothelial growth factor (VEGF) and angiogenin (ANG) have been shown to be significantly upregulated in HNSCC. Among them, ANG is unique in which it is a ribonuclease that regulates ribosomal RNA (rRNA) transcription. ANG-stimulated rRNA transcription has been shown to be a general requirement for angiogenesis induced by other angiogenic factors. ANG inhibitors have been demonstrated to inhibit angiogenesis and tumor growth induced not only by ANG but also by other angiogenic factors. As the role of ANG in HNSCC is being unveiled, the therapeutic potential of ANG inhibitors in HNSCC is expected.
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PMID:Angiogenin-mediated ribosomal RNA transcription as a molecular target for treatment of head and neck squamous cell carcinoma. 2065 48

Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelial-mesenchymal transition (EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-to-epithelial transition (MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be the preferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT (TFs) and the miRNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and miRNAs, where miRNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of miRNA biogenesis, the ribonuclease type III endonuclease Dicer plays a central role in EMT-TFs/miRNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.
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PMID:Epithelial-mesenchymal transition transcription factors and miRNAs: "Plastic surgeons" of breast cancer. 2511 47

We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins-a low immunogenic variant of Pseudomonas aeruginosa exotoxin A and ribonuclease Barnase from Bacillus amyloliquefaciens. The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins). We have shown that both target agents efficiently accumulate in the tumor. Simultaneous treatment of breast carcinoma-bearing mice with anti-EpCAM fusion toxin based on LoPE and HER2-specific liposomes loaded with Barnase leads to concurrent elimination of primary tumor and metastases. Monotherapy with anti-HER2- or anti-EpCAM-toxins did not produce a comparable effect on metastases. The proposed approach can be considered as a promising strategy for significant improvement of cancer therapy.
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PMID:Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape. 3308 7


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