The novel mechanism of lenalidomide activity.
نویسندگان
چکیده
Lenalidomide acts by a novel drug mechanism-modulation of the substrate specificity of the CRL4(CRBN) E3 ubiquitin ligase. In multiple myeloma, lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4(CRBN). Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells. In del(5q) myelodysplastic syndrome, lenalidomide induces the degradation of CK1α, which preferentially affects del(5q) cells because they express this gene at haploinsufficient levels. In the future, modulation of ubiquitin ligase function may enable us to target previously "undruggable" proteins.
منابع مشابه
Low Dose of Lenalidomide Enhances NK Cell Activity: Possible Implication as an Adjuvant
Background: Lenalidomide, a synthetic immunomodulatory drug, has a wide range of features including anti-angiogenic and anti-proliferative properties. To date, researchers have shown that lenalidomide is capable of ameliorating the immune system factors and antitumor responses. Most researchers have reported that lenalidomide enhances the immune response in certain cancer patients through sever...
متن کاملBlood Spotlight The novel mechanism of lenalidomide activity
Lenalidomide is a highly effective treatment for multiple myeloma, other B-cell neoplasms including mantle cell lymphoma and chronic lymphocytic leukemia, and myelodysplastic syndrome (MDS) with del(5q). Lenalidomide is a derivative of thalidomide, infamous for its teratogenicity following use as an anti-emetic in pregnant women. Thalidomide, lenalidomide, and another derivative, pomalidomide (...
متن کاملLenalidomide in the Treatment of Chronic Lymphocytic Leukemia
The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and s...
متن کاملبررسی اثر داروی ضد سرطانی پومالیدومید بر فعالیت حیاتی و القای آپوپتوز سلول‌های تک هسته‌ای مغز استخوان
Background and Objective: Pomalidomide - a combination of Lenalidomide and Thalidomide drugs- is one of the newest anticancer drugs. Pomalidomide induces apoptosis in cancer cells. Furthermore, few studies indicating its relatively low cytotoxic effects on normal peripheral blood cells have been carried out. However, there is yet no information about the effects of Pomalidomide on bone marrow c...
متن کاملNovel insights into the mechanism of action of lenalidomide
Editorial Lenalidomide (Revlimid ®) is a synthetic derivative of thalidomide (Thalomid ®) currently licensed by the US Food and Drug Administration (FDA) and other international regulatory agencies for the treatment of multiple myeloma (MM) (in combination with dexamethasone) 1-3 and low or intermediate-1 risk myelodysplastic syndromes bearing 5q cytogenetic abnormalities (as a standalone agent...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 126 21 شماره
صفحات -
تاریخ انتشار 2015