Publications by authors named "Lorenza Fusi"
Forkhead box O (FoxO) transcription factors are conserved proteins involved in the regulation of life span and age-related diseases, such as diabetes and cancer. Stress stimuli or growth factor deprivation promotes nuclear localization and activation of FoxO proteins, which-depending on the cellular context-can lead to cell cycle arrest or apoptosis. In endothelial cells (ECs), they further regulate angiogenesis and may promote inflammation and vessel destabilization implicating a role of FoxOs in vascular diseases.
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- The MEK5/ERK5 MAPK cascade is activated by various stimuli such as growth factors and stress, functioning mainly in the endothelium to protect against mechanical stress and support tissue integrity in bone, cartilage, and muscle.
- This pathway is linked to multiple health issues, particularly in cancer, where it helps tumor cells survive under stress from treatments, and also contributes to cardiovascular diseases like atherosclerosis.
- The text emphasizes the dual role of the MEK5/ERK5 pathway in both protecting healthy tissues and fostering therapy resistance in cancers, suggesting it could be a potential target for cancer treatments while also considering the risks involved.
Cutaneous melanoma is a highly malignant tumor typically driven by somatic mutation in the oncogenes BRAF or NRAS, leading to uncontrolled activation of the MEK/ERK MAPK pathway. Despite the availability of immunotherapy, MAPK pathway‒targeting regimens are still a valuable treatment option for BRAF-mutant melanoma. Unfortunately, patients with NRAS mutation do not benefit from such therapies owing to the lack of targetable BRAF mutations and a high degree of intrinsic and acquired resistance toward MEK inhibition.
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