Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer. Although the useful of some molecular-targeted agents as first-line therapies has been investigated, none have been found to exert satisfactory efficacy. In this article, we report the results of a Phase II study of selumetinib in patients with metastatic biliary cancer. Selumetinib is an inhibitor of MEK1/2 targeting the RAS/RAF/MEK/extracellular signal-related kinase pathway. Three out of 28 patients showed a confirmed partial response, representing a response rate of 12%. The median progression-free survival was 3.7 months and the median overall survival was 9.8 months. The most common toxicities were rash, xerostomia and nausea. Most toxicities were grade 1 or 2, and the most common grade 3/4 toxicities were diarrhea and nausea. All toxicities were manageable and reversible. The results warrant further evaluation of the use of selumetinib in patients with metastatic biliary cancer.
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PMID:Inhibitor of MEK1/2, selumetinib, for biliary tract cancer. 2151 26

Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25-85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients' quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.
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PMID:Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails. 3037 1