High-througput genomic and transcriptomic profiling of tumor tissue and/or liquid biopsies enable the identification of molecular signatures useful for cancer subtyping, (minimally invasive) early detection of malignant lesions and prediction of tumoral progression/response to therapy/survival. My lab is involved in research/clinical protocols with patiens with breast or prostate cancer as well as in research studies on melanoma or oropharynx, ovarian, pancreatic cancer. Both experimental and data analysis/elaboration/management approaches are undertaken within an interdisciplinary environment. A large collection of blood and information regarding life-styles, smoke/alcohol habit, stress management, familial history, hormonal/reproductive history, etc, has been realized within a breast cancer screening context. A new research protocol on melanoma is about to start with both primary tissue and blood collection.
We aim at identifying circulating biomarkers for minimally invasive early detection of BC and prediction of melanoma recurrence (ESR14, 15). These approaches will help in identifying new strategies for BC and melanoma prevention as well as in personalizing mammographic screening and melanoma therapy.
Project 14 – Analysis of circulating biomarkers for minimally invasive early detection of Breast Cancer (BC)
Hypothesis: BC screening programs allow early disease detection, but they have drawbacks. Appropriate risk stratification would lead to personalized screening programs tailored on individual risk.
Background and Significance: Although mammography has become standard of care in BC screening, its limitations are well recognized (overdiagnosis, the use of ionizing radiation, poor accuracy in women with dense breast tissue, a relatively high rate of false positives, and personal discomfort). In addition, the current screening protocols are based on women age only, ignoring other risk factors and defining a single screening periodicity within pre-specified age ranges. Circulating biomarkers analysis and SNP assessment together with evaluation of modifiable risk factors, breast density and well known factors, could help in a better definition of individual BC risk.
Objectives: to provide comprehensive training on BC prevention to ESR14 who will work inside a private non-profit foundation that manages several primary and secondary prevention programs, especially for BC. In particular, ESR14 will be involved in the Andromeda project to tailor BC screening according to life-styles and genetic risk and will be trained on the analysis of circulating-free microRNAs (cf-miRNA) to detect BC or predict BC risk as well as on the evaluation of polygenic risk score from multiple SNPs assessment.
Project 15 – Analysis of circulating biomarkers for early detection of melanoma recurrence.
Hypothesis: Identification of non-invasive biomarkers to monitor patients after surgical resection of localized primary cutaneous malignant melanoma (CMM) is fundamental for the detection of early clinical recurrence.
Background and Significance: Men and women exhibit different age patterns of melanoma incidence and different prognosis. Women are often diagnosed during their reproductive years and have a better prognosis that is not completely explained by differences in the stage at diagnosis or in the biology of the lesions. Large amount of expression profiles is available in public repositories and could be investigated with a special focus on gender-specific prognostic signatures according to age classes. At the same time, collection of primary lesion tissues and of longitudinal serum/plasma samples together with patient follow-up could allow prospective validation of prognostic signatures and identification of novel circulating markers to monitor patients.
Objectives: To look for gender and age-specific markers of melanoma recurrence by focussing on meta-analysis of expression profiles of CMM primary lesions and ensuing clinical history (recurrent free versus metastatic disease, response to treatment, 5 years survival) integrated with information of circulating sex hormone levels and miRNAs (cf-miRNAs). To establish a data base of longitudinal levels of sex hormones and cf-miRNAs from plasma/serum samples collected from patients surgically treated for localized primary CMM.
 Nosrati, A. & Wei, M. L. Sex disparities in melanoma outcomes: the role of biology. Arch Biochem Biophys 563, 42-50 (2014).
 Marzagalli, M. et al. Estrogen Receptor beta in Melanoma: From Molecular Insights to Potential Clinical Utility. Front Endocrinol 7, 140 (2016).
 Giordano, L. et al. The ANDROMEDA prospective cohort study: predictive value of combined criteria to tailor breast cancer screening and new opportunities from circulating markers: study protocol. BMC Cancer 17, 785, 5 (2017).
 Mavaddat, N. et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet 104, 21-34, (2019),
 Hamam, R. et al. Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis 8, e3045 (2017).
 Mello-Grand, M. et al. Circulating microRNAs combined with PSA for accurate and non-invasive prostate cancer detection. Carcinogenesis (2018).