Assessment of Retinal Pigment Epithelium Alterations and Chorioretinal Vascular Network Analyses in Patients under Treatment with BRAF/MEK Inhibitor for Different Malignancies: A Pilot Study

Abstract

In the last two decades, an increasing number of so-called molecular-targeted therapies have become available for the treatment of patients with advanced malignancies. These drugs have included inhibitors of proteins in the MAPK pathway, such as BRAF and MEK inhibitors, which are characterized by a distinct toxicity profile. The eye is particularly susceptible to adverse effects due to MEK inhibitors, and the term MEKAR (MEK-inhibitor-associated retinopathy) indicates the presence of subretinal fluid, mimicking central serous chorioretinopathy (CSC). The pathogenesis of the retinal alterations related to MAPK pathway inhibitors is still unclear, and questions are still open. The present study aims to assess the presence of retinal pigment epithelium alterations as predictive parameters for retinal toxicity, analyzing, at the same time, the chorioretinal vascular network in patients undergoing BRAF/MEK inhibitor treatment for different malignancies.

PROTACs: A novel strategy for cancer drug discovery and development

“…MEK1 and MEK2 (mitogen activated protein kinase) are two family members of MAP kinase, which are important signaling molecules in the Ras–RAF–MEK–ERK pathway 288 . MEK1 and MEK2 activate downstream ERK to promote growth and survival of cancer cells, thus playing an important role in tumor development 289,290 …”

“…288 MEK1 and MEK2 activate downstream ERK to promote growth and survival of cancer cells, thus playing an important role in tumor development. 289,290 The Jin group has been engaged in the discovery of a variety of MEK degraders based on VHL and CRBN E3 ligands. Specifically, in 2020 the group reported several novel and potent VHL recruited MEK1/2 degraders, and the first CRBN recruited MEK1/2 degrader MS910 (Table 1).…”

“… 288 MEK1 and MEK2 activate downstream ERK to promote growth and survival of cancer cells, thus playing an important role in tumor development. 289 , 290 …”