AZD6244, also known as selumetinib, is an investigational medication developed by AstraZeneca. It represents a targeted therapy, focusing on specific molecular pathways involved in disease progression. This drug has been extensively researched for its potential applications in various medical conditions.
How AZD6244 Works
AZD6244 functions as a MEK inhibitor, targeting MEK1 and MEK2 proteins. These proteins are part of the mitogen-activated protein kinase (MAPK) pathway, a signaling network controlling cell growth, division, and survival. In many cancers, this pathway becomes overactive due to genetic mutations, leading to uncontrolled cell proliferation.
By inhibiting MEK1 and MEK2, AZD6244 prevents them from activating downstream proteins like ERK1/2. This disruption blocks the transmission of growth signals from the cell surface to the nucleus. Consequently, this targeted action can slow or halt the growth of certain cancer cells and promote their programmed death, a process known as apoptosis.
Conditions Treated with AZD6244
AZD6244 has been investigated for its potential to treat various cancers. It has been studied in melanoma, particularly in tumors with BRAF V600E mutations, and in non-small cell lung cancer (NSCLC). Its efficacy in these cancers is linked to mutations in the RAS/RAF/MEK/ERK pathway.
The drug has also been explored for its use in pancreatic and colorectal cancers, where KRAS gene mutations are common. AZD6244 has shown promise in treating plexiform neurofibromas (PNs), which are tumors that grow along nerves in individuals with Neurofibromatosis type 1 (NF1). It is frequently studied in combination with other anti-cancer drugs to enhance therapeutic outcomes.
Current Research and Clinical Findings
AZD6244 has advanced through various phases of clinical trials. In a Phase II trial involving children with NF1 and inoperable plexiform neurofibromas, over 50% of enrolled patients experienced a decrease in tumor volume.
Common side effects reported in clinical studies include:
Rash
Diarrhea
Fatigue
Nausea
Vomiting
Abdominal pain
Dry skin
Musculoskeletal pain
Elevated liver enzymes
Acneiform rash
Paronychia
Peripheral edema
AZD6244 received FDA approval on April 10, 2020, for the treatment of symptomatic, inoperable plexiform neurofibromas in pediatric patients aged two years and older with NF1, based on findings from the SPRINT trial.