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Table of contents
LIST OF ABBREVIATIONS
LIST OF FIGURES AND TABLES
INTRODUCTION
I. Fibrosis and cancer
1) Myofibroblasts in wound healing and fibrosis
Wound healing
Fibroblast to myofibroblast transition
Myofibroblasts origin
Pathogenesis of fibrosis
-Cell-autonomous mechanisms: activation of pro-fibrotic signaling pathways
-Non-cell-autonomous mechanisms: the extracellular matrix as a driver of fibrosis
2) Cancer as an over-healing wound
a) Molecular and cellular composition of the tumor microenvironment
Myofibroblasts in cancer: cancer-associated fibroblasts definition and origin
Cancer-associated fibroblasts in tumor initiation and progression
d) Targeting cancer-associated fibroblasts as a therapeutic strategy
Chronic inflammation in tumor initiation and progression
Anticancer therapy-induced fibrosis
Anti-fibrotic therapies in the treatment of cancer
II. Melanoma
1) Epidemiology
2) Risk factors
a) Genetics of melanoma
b) Environmental factors
3) Origin
a) Melanocytes
b) Melanomagenesis
c) Driver mutations
d) Melanoma heterogeneity
4) Clinical management
a) Targeted therapies
b) Immunotherapies
5) Resistance to MAPK-targeted therapies
a) Intrinsic resistance
b) Genetic mechanisms of acquired resistance
c) Non-genetic mechanisms of acquired resistance
-Cell-intrinsic mechanisms of resistance
-Cell-extrinsic mechanisms of resistance
1) Therapy-induced fibrotic remodeling of the tumor microenvironment
2) Therapy-induced cytoskeleton remodeling
3) Therapy-induced inflammation
III. microRNAs
1) Non-coding RNAs
a) Definition and classification
b) miRNAs nomenclature
2) Biogenesis
a) Transcription
b) Maturation
3) Mechanisms of action
4) MiRNAs-based therapies
a) miRNAs inhibition
b) miRNAs replacement
c) miRNAs as diagnostic and prognostic biomarkers
5) MiRNAs in fibrosis: fibromiRs
6) MiRNAs in cancer: oncomiRs
a) MiRNAs in melanoma
b) MiRNAs and melanoma resistance to MAPK-targeted therapies
7) The miR-143/145 cluster: a profibrotic locus with a controversial role in cancer
a) Structure, conservation, expression regulation
b) miR-143/145 cluster in fibrosis
c) miR-143/145 in cancer
-Molecular targets of the cluster in cancer
RESULTS
I. Research context and aims
II. Scientific article
DISCUSSION
CONCLUSIONS
AND PERSPECTIVES
BIBLIOGRAPHY
