Modeling and Targeting Metastatic Cancer
The Lanfrancone Lab investigates how fundamental biological processes regulate metastasis dissemination and which are the driving forces beyond this phenomenon. We combine genetic and functional approaches to investigate how cancer cells react to microenvironmental cues, survive, proliferate and disseminate to distant organs. In particular, we are interested in elucidating the key molecular pathways involved in the progression from a non-invasive, locally-growing, to an aggressive, therapy-resistant metastatic tumor. Central molecular pathways converge on key cellular functions, including self-renewal, proliferation, migration and differentiation. Our hypothesis is that changes in chromatin status and metabolism can impact on the pathogenesis of cancer, as genetic alterations do, and that drug resistance can be overcome through the induction of chemo-sensitivity by inhibition of selective epigenetic and metabolic pathways and/or the use of combinatorial therapies and drug repurposing.
Our ongoing aims are:
- Identification of actionable candidates in therapy-resistant metastatic melanomas by in vivo and in vitroshRNA screens.
- Modelling of the metastatic process in vivo and in vitro, to identify and target, genes and pathways involved in dissemination.
- Reprogramming of the metastatic phenotype.
- Combinatorial drug testing in vitro and in vivo.
- Development of a novel, multifunctional nanomedicine to target and ablate melanoma lesions.
Most Relevant Publications
Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors.
Cell Rep, 2022
Long non-coding RNA TINCR suppresses metastatic melanoma dissemination by preventing ATF4 translation.
EMBO Rep, 2021
ShcD Binds DOCK4, Promotes Ameboid Motility and Metastasis Dissemination, Predicting Poor Prognosis in Melanoma.
Cancers (Basel), 2020
In Vivo Genetic Screens of Patient-Derived Tumors Revealed Unexpected Frailty of the Transformed Phenotype.
Cancer Discov, 2016