Research project

Improving therapy for breast cancer and melanoma by transcriptome-methylome profiling, integrative network inference, and design of novel theranostic tools ITT (DSB.AD006.123)

Thematic area

Biomedical sciences

Project area

Biologia Molecolare/Cellulare (DSB.AD006)

Structure responsible for the research project

Institute of clinical physiology (IFC)

Other structures collaborating in the research project

Project manager

CATERINA CINTI
Phone number: 0577381294
Email: caterina.cinti@ifc.cnr.it

Abstract

Gene expression is modulated by multiple complex mechanisms, including epigenetic regulation. DNA methylation is thought to play a major role in tumorigenesis and cancer progression. Molecular profiling of coupled transcriptome and methylome can capture dynamics specifically correlated with disease states, and naturally complemented by interactomic data.The complexity of finding cancer profiles suggests that signatures of dysregulation involve possible interplay between protein coding genes and non-coding RNAs, whose mechanisms are yet to be understood. Our proposal addresses these challenging problems with regard to metastatic breast and melanoma cancers, two cancer having generally poor prognosis. Notably, the molecular events which lead to unresponsiveness are yet unknown, although hypermethylation of many genes in these malignant cancers has offered a strong rationale for treatment approaches based on the use of demethylating agents(DAC). An efficient combined therapeutic strategy with DAC and novel theranostic tools, which knock-down overexpressed oncogenes, will be done. The expected impact is an acceleration of therapeutic signatures to clinical applications.

Goals

Epigenetics accounts for about half of gene-inactivating events occurring in cancer. In contrast to gene mutations, the latter can be modulated or reversed by drugs targeting epigenetic mechanisms. In order to understand what molecular mechanisms are behind development and progression, we believe that a central role is played by epigenetic modification in BC and MEL cancer. We propose the design and implementation of an integrative approach to personalized medicine. One of the most profound changes to medicine is the movement toward tailored therapeutics, which uses genomic information - in addition to family history, lifestyle, and environmental factors - to customize health management. By combining genomic and clinical information, more accurate predictions can be made about a person's susceptibility of developing disease, the course of disease, and response to treatment. In order to reach these goals, the research project will extend our currently ongoing studies with the aim of elucidating a multilevel approach to epigenetic and therapy applied to multiple subtypes of infiltrating and metastatic BC and MEL cancer.

Start date of activity

03/06/2015

Keywords

Computational System Biology, Omics, Cancer

Last update: 28/03/2024