Conferinţa Diaspora în Cercetarea Ştiinţifică şi Invăţământul Superior din România, Timisoara, 2016 Principii de medicina personalizata in melanomul cutanat 1 Workshop - Perspective în medicina personalizată – de la concept la aplicaţii clinice Monica Neagu 1,2 , Carolina Constantin 1 1 Laborator Imunologie, Institutul Național de Patologie “Victor Babeş”, București, Romania (e-mail: [email protected]) 2 Facultatea de Biologie, Universitatea București, Romania Institutul National “Victor Babes” Institutul National “Victor Babes” www.ivb.ro 99-101 Splaiul Independentei, 050096, Bucharest, Romania
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Principii de medicina personalizata in melanomul cutanat2 Facultatea de Biologie, Universitatea București,Romania Institutul National “Victor Babes” 99-101 Splaiul Independentei,
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Conferinţa Diaspora în Cercetarea Ştiinţifică şi Invăţământul Superior din România, Timisoara, 2016
Principii de medicina personalizata in melanomul cutanat
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Workshop - Perspective în medicina personalizată – de la concept la aplicaţii clinice
Monica Neagu 1,2, Carolina Constantin1
1 Laborator Imunologie, Institutul Național de Patologie “Victor Babeş”, București, Romania
melanomul cutanat are cea mai mare rată a mutațiilor
100 - 120 mutații / megabază
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Istoria Istoria terapieiterapiei •Melphalan
•Dacarbazina
•2001 – imatinib pentru leucemia cronica mieloida !!
• modificarile genetice care stau la baza patogenezei melanomului pot sa
fie tinte terapeutice
• 2002 - mutatiile NRAS si proteina downstream BRAF sunt descoperite
mutatia BRAF in 50% din cazuri, 80 % substitutia valinei cu acidul
glutamic (V600E) “discovery of BRAFV600E has proven to be a turning point for melanoma treatment”
• Sorafenib – insucces
• Vemurafenib – 2011 FDA
•2015 combinatie dabrafenib (inhibitor de BRAF de a 2-a generatie) cu
trametinib (inhibitor de MEK) – supravietuire crescuta
•Imunoterapie personalizata
EEvolutivolutia a publicatiilorpublicatiilor
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0
100
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1960 1970 1980 1990 2000 2010 2020
Publication count 800
““Immune therapy and melanomaImmune therapy and melanoma””
ImunoterapiaImunoterapia in in melanommelanom Melanom – tumora cu potential imunogenic crescut 1987 – prima publicatie cu TIL
Imunoterapia in melanom a inceput cu 1992 - FDA doze crescute de IL-2
4 Neagu M. The immune system - a hidden treasure for biomarker discovery in cutaneous melanoma. Adv Clin Chem, 2012; 58 : 89-140
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Monica Neagu and Carolina Constantin, New Insights in Cutaneous Melanoma Immune-Therapy — Tackling Immune-Suppression and Specific Anti-Tumoral Response, Melanoma - Current Clinical Management and Future Therapeutics, Prof. Mandi Murph (Ed.), InTech, 2015, DOI: 10.5772/59494.
ImunoterapiaImunoterapia in in melanommelanom
7 noi medicamente aprobate din care 4 (ipilimumab, nivolumab,
pembrolizumab si talimogene laherparepvec) actiune directa pe sistem imun, iar
Monica Neagu, The immune system - a hidden treasure for biomarker discovery in cutaneous melanoma, In Gregory S. Makowski, editor: Advances in Clinical Chemistry, Burlington: Academic Press vol 58, 2012 pp. 89-140, ISBN: 978-0-12-394383-5
Monica Neagu, Carolina Constantin, Sabina Zurac, Immune parameters in prognosis and therapy monitoring of cutaneous melanoma patients - experience, role and limitations, BioMed Research International, special issue Molecular Biomarkers: Tools of Medicine (MBTM) Volume 2013, 15 November 2013 Article ID 107940
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BiomarkeriBiomarkeri circulanticirculanti –– orienteazaorienteaza terapiaterapia IL-8 – vit D
Ene CD, Anghel AE, Neagu M, Nicolae I, 25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression. Mediators Inflamm. 2015;2015:904876. doi: 10.1155/2015/904876.
25-OH vitamin D3 (ng mL−1) serum level in melanoma patients for individuals with normal and high serum IL-8 (pg mL−1). Prevalence depicts the subgroups of melanoma patients with high serum IL-8 congregating in the low serum 25-OH vitamin D3 ranges.
HeterogeneitateaHeterogeneitatea tumoralatumorala
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Monica Neagu, Carolina Constantin, Sabina Zurac, Immune parameters in prognosis and therapy monitoring of cutaneous melanoma patients - experience, role and limitations, BioMed Research International, special issue Molecular Biomarkers: Tools of Medicine (MBTM) Volume 2013, 15 November 2013
HeterogenHeterogeneeitateaitatea tumoralatumorala
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Sabina Zurac, Monica Neagu et al, Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors, Oncology Lett, 11: 3354-3360, 2016
In In practicpractica a –– medicina demedicina de precipreciziezie
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Modele experimentale noi – tinte imuno, tinte de semnalizare intracelulara corelate cu particularitatile genetice individuale
M. Neagu, C. Constantin, C. Tanase, Immune-related biomarkers for diagnosis/prognosis and therapy monitoring of cutaneous melanoma, Expert Rev. Mol. Diagn. 10 (7) (2010) 897–919.
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Carolina Constantin, PhD
Thank you! Thank you! MultumescMultumesc!!
Prof. Sabina Zurac – Spitalul Colentina, Bucuresti
Dr. Amalia Anghel – SkinMed, Bucuresti
Dr. Ilinca Nicolae - Spitalul Victor Babes, Bucuresti
Centrului de Excelenta in Dermato-oncologie – UMF Carol Davila