Mechanisms of tumor progression

Therapeutic exploitation of human melanoma cell addiction to LOXL3

Background

Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes. Extensive work by our lab and others has established the deregulation of lysyl oxidases in cancer and their status has been associated with patient outcome in specific neoplasias. Regarding LOXL3, we have recently unveiled an unexpected contribution of LOXL3 to melanoma pathogenesis. Our studies reveal that LOXL3 is upregulated in human melanoma samples from primary and metastatic origin and LOXL3 contributes to melanomagenesis. Besides, human melanoma cells are addicted to LOXL3 expression since LOXL3 knockdown halts cell proliferation and triggers apoptosis. Thereafter, our results support the relevance of LOXL3 as a novel druggable target for therapeutic intervention in this severe disease.

Hypothesis

The deletion of LOXL3 drastically stops melanoma cell proliferation. We propose to use small molecule inhibitors to target LOXL3 in melanoma cells and test their efficacy at inactivating LOXL3 and promoting melanoma cell death. Subsequently, we will establish the suitable conditions for their use in in vivo preclinical models.