The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.
The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.
The blood flow in the pectoral branch of the thoracoacromial artery runs through the choke vessels that dilate at the elevation of the pectoralis major myocutaneous flap, first into the fourth intercostal perforating branches; then to the anastomotic vascular network of the fourth, fifth, and sixth intercostal perforating branches; and finally to reach the periphery of the skin island.
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