What is an LSD1 inhibitor?
LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival.
What medication was approved for acute myeloid leukemia?
The US Food and Drug Administration (FDA) has approved 2 new drugs, Daurismo (glasdegib) and Venclexta (venetoclax), to treat people newly diagnosed with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy.
Is sorafenib approved for AML?
Sorafenib is FDA-approved in the United States for solid tumor patients of various types. However, it is not FDA-approved for acute myeloid leukemia. Nonetheless, it has been tested in patients with FLT3 mutations and in AML in general.
What is Bomedemstat?
Bomedemstat, is a new oral (taken by mouth) medication that works by turning off the activity of an enzyme called LSD1 (lysine specific demethylase 1) which is present at low levels in cells of all people.
What do histone Demethylases do?
The histone demethylases are involved in regulating cellular processes such as chromatin structure and transcription. They are important for normal embryonic development and are involved in diseases such as cancer. Both histones and non-histone proteins are targets for the histone demethylases.
What is the latest treatment for acute myeloid leukemia?
The Food and Drug Administration (FDA) recently approved two new treatments for some adult patients with acute myeloid leukemia (AML): enasidenib (Idhifa®), a drug that targets aberrant forms of the IDH2 protein; and liposomal cytarabine-daunorubicin CPX-351 (Vyxeos™), a two-drug chemotherapy combination encapsulated …
How do FLT3 inhibitors work?
All FLT3 inhibitors interact with the ATP-binding site of the intracellular TKD and competitively inhibit ATP binding, thereby preventing receptor autophosphorylation and activation of downstream signaling.
When was sorafenib approved for HCC?
The U.S. Food and Drug Administration (FDA) on November 19 announced that it has approved sorafenib (Nexavar) for use in patients with hepatocellular carcinoma (HCC) when the cancer is inoperable. Sorafenib was originally approved in 2005 for the treatment of patients with advanced renal cell carcinoma.
What are the side effects of sorafenib?
Side Effects
- Bleeding gums.
- blistering, peeling, redness, or swelling of the palms of the hands or bottoms of the feet.
- bloating of the abdomen or stomach.
- blood in the urine or stools.
- clay-colored stools.
- coughing up blood.
- difficulty with breathing or swallowing.
- increased menstrual flow or vaginal bleeding.
Is thrombocythemia a blood disorder?
Overview. Essential thrombocythemia (throm-boe-sie-THEE-me-uh) is an uncommon disorder in which your body produces too many platelets. Platelets are the part of your blood that sticks together to form clots. This condition may cause you to feel fatigued and lightheaded and to experience headaches and vision changes.
What does acetylation of histones do?
Histone acetylation is a critical epigenetic modification that changes chromatin architecture and regulates gene expression by opening or closing the chromatin structure. It plays an essential role in cell cycle progression and differentiation.
How does LSD1 inhibition exert its anti-leukemic effect in AML?
Cusan M, Cai SF, Mohammad HP, Krivtsov A, Chramiec A, Loizou E, et al. LSD1 inhibition exerts its anti-leukemic effect by recommissioning PU.1- and C/EBPalpha-dependent enhancers in AML. Blood (2018) 131(15):1730–42.10.1182/blood-2017-09-807024 [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] 63.
Can LSD1 inhibitors and all-trans retinoic acid reactivate myeloid differentiation?
To date, the most promising application of this therapeutic strategy appears to be combination therapy of LSD1 inhibitors with all-trans retinoic acid (ATRA) to reactivate myeloid differentiation in cells that are not spontaneously susceptible to ATRA treatment.
What is the mechanism of action of a novel LSD1 inhibitor t-3775440?
A novel LSD1 inhibitor T-3775440 disrupts GFI1B-containing complex leading to transdifferentiation and impaired growth of AML cells. Mol Cancer Ther (2017) 16(2):273–84.10.1158/1535-7163.MCT-16-0471 [ PubMed] [ CrossRef] [ Google Scholar]
Does LSD1 play a role in tumorigenesis?
After an initial characterization of the function of LSD1 in embryonic development, a number of studies have described LSD1 as implicated in tumorigenesis, and found it overexpressed in many solid tumors, where it impairs differentiation, promotes proliferation, cell motility and invasiveness, and associates with poor prognosis ( 9 – 13 ).