Dott.ssa Valentina Monica

f402-c402 Dottorato in Scienze Biomediche ed Oncologia
Dottorato: 24° ciclo
Matricola: 316488

Tesi di dottorato

MOLECULAR MARKERS WITH DIAGNOSTIC, PROGNOSTIC AND/OR PREDICTIVE ROLE IN LUNG CARCINOMA

Tutor: Marco Volante

Relatore: Mauro Papotti

Data discussione tesi: 15/03/2013

La mia tesi di dottorato riguarda, principalmnete, lo studio del carcinoma polmonare non a piccole cellule e, principalmente, include analisi relative aIl’espressione di marcatori molecolari a scopo diagnostico e prognostico/predittivo, in linee cellulari immortalizzate, tessuti fissati in formalina e inclusi in paraffina, tessuti congelati.

Il carcinoma polmonare è la principale causa di morte per cancro nel mondo e in Europa conta circa 500.000 casi ogni anno. In una patologia eterogenea come il carcinoma polmonare, caratterizzato dalla presenza di istotipi differenti, la precisione della diagnosi patologica procede in parallelo con la scelta del trattamento più efficace. Un biomarcatore può avere valenza prognostica, diagnostica o predittiva e tale ruolo è spesso legato all’istotipo tumorale. Risultati recenti suggeriscono un crescente interesse verso la ricerca volta alla determinazione di mappe molecolari istotipo-specifiche, in tessuti pre-neoplastici, che incrementino la comprensione del rischio di sviluppo della patologia tumorale e la possibilità di utilizzo di agenti chemiopreventivi. L’importanza dell’assetto biomolecolare nella patologia ha portato ad un incremento dello sviluppo di farmaci antitumorali a bersaglio molecolare a scopo preventivo e terapeutico. Risultati promettenti ottenuti dai trials clinici identificano uno spettro di terapie mirate comprendenti:

- piccole molecole a funzione inibitoria, dirette verso recettori chiave ad attività tirosino-chinasica o dirette verso specifici siti di legame enzimatici;

- anticorpi monoclonali in grado di bloccare l’interazione ligando-recettore ai fini di inibire determinate vie di segnale intracellulare.

L’utilizzo di agenti terapeutici di nuova generazione è collegato allo sviluppo ed alla validazione di biomarcatori in grado di definirne e predirne l’efficacia.

Attività di ricerca




					Articles
					

					Abstracts/Poster/Oral Presentations

Polymerase eta mRNA expression predicts survival of non-small cell lung cancer patients treated with platinum-based chemotherapy.

Ceppi P, Novello S, Cambieri A, Longo M, Monica V, Lo Iacono M, Giaj-Levra M, Saviozzi S, Volante M, Papotti M, Scagliotti G.

Clin Cancer Res. 2009 Feb 1;15(3):1039-45.

Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung.

Monica V, Ceppi P, Righi L, Tavaglione V, Volante M, Pelosi G, Scagliotti GV, Papotti M.

Mod Pathol. 2009 May;22(5):709-17. Epub 2009 Mar 13.

Effects of Src kinase inhibition induced by dasatinib in non-small cell lung cancer cell lines treated with cisplatin.

Ceppi P, Papotti M, Monica V, Lo Iacono M, Saviozzi S, Pautasso M, Novello S, Mussino S, Bracco E, Volante M, Scagliotti GV.

Mol Cancer Ther. 2009 Nov;8(11):3066-74. Epub 2009 Oct 27.

Differential Thymidylate Synthase Expression in Different Variants of Large-Cell Carcinoma of the Lung.

Monica V, Scagliotti GV, Ceppi P, Righi L, Cambieri A, Lo Iacono M, Saviozzi S, Volante M, Novello S, Papotti M.

Clin Cancer Res. 2009 Dec 15;15(24):7547-7552. Epub .

p63 and p73 isoform expression in non-small cell lung cancer and corresponding morphological normal lung tissue.

Lo Iacono M, Monica V, Saviozzi S, Ceppi P, Bracco E, Papotti M, Scagliotti GV.

J Thorac Oncol. 2011 Mar;6(3):473-81.

Aurora Kinase A expression is associated with lung cancer histological-subtypes and with tumor de-differentiation.

Lo Iacono M, Monica V, Saviozzi S, Ceppi P, Bracco E, Papotti M, Scagliotti GV.

J Transl Med. 2011 Jun 30;9:100.

Heterogeneity of large cell carcinoma of the lung: an immunophenotypic and miRNA-based analysis.

Barbareschi M, Cantaloni C, Del Vescovo V, Cavazza A, Monica V, Carella R, Rossi G, Morelli L, Cucino A, Silvestri M, Tirone G, Pelosi G, Graziano P, Papotti M, Dalla Palma P, Doglioni C, Denti MA.

Am J Clin Pathol. 2011 Nov;136(5):773-82.

Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer.

Shaw AT, Varghese AM, Solomon BJ, Costa DB, Novello S, Mino-Kenudson M, Awad MM, Engelman JA, Riely GJ, Monica V, Yeap BY, Scagliotti GV.

Ann Oncol. 2012 Aug 10. [Epub ahead of print]

Role of hormone receptor expression in patients with advanced-stage lung cancer treated with chemotherapy.

Monica V, Longo M, Felice B, Scagliotti GV, Papotti M, Novello S.

Clin Lung Cancer. 2012 Nov;13(6):416-23. doi: 10.1016/j.cllc.2012.03.006. Epub 2012 Jun 2.

Monica V, Solero A, Orso F, Corà D, Re A, Sessa R, Sismondi P, De Bortoli M, Primo L, Caselle M, Taverna D. “miRNA expression in breast cancer” . Molecular Determinants of Cell Signalling- III Seminario Nazionale SIBBM. MBC Center, june 25-27 2007, Torino.

Scagliotti G.V, Monica V, Ceppi P, Righi L, Cambieri A, Volante M, Novello S, Capelletto E, Papotti M. “Baseline thymidilate synthase expression according to histological subtypes in early stage Non-Small Cell Lung Cancer.” 2009 ASCO Annual Meeting. Lung Cancer- Local Regional Adjuvant Therapy. Poster Discussion Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 7521)

Scagliotti G.V, MonicaV, Ceppi P, Righi L, Cambieri A, Lo Iacono M, Saviozzi S, Volante M, Novello S, Papotti M. “Thymidilate Synthase expression in Large Cell Carcinoma of the Lung” 13th World Conference on lung cancer, July 31- August 4, San Francisco (CA, USA) Prognostic and predictive Markers- pharmacogenomic markers.

Monica V, Novello S, Longo M, Cappia S, Pandiscia S, Crida B, Giaj Levra M, Rapetti G.S, Capelletto E, Papotti M. “Sex-linked hormone receptor expression in lung cancer patients: pilot study in a consecutive group of patients with advanced Lung Cancer.” 13th World Conference on lung cancer, July 31- August 4, San Francisco (CA, USA) Prognostic and predictive Markers

Lo Iacono M, Ceppi P, Saviozzi S, Monica V, Pandiscia S, Billè A, Bracco E, Papotti M and Scagliotti G.V.“Expression Patterns of p53 family N-terminal isoforms in Non-small cell lung cancer” 13th World Conference on lung cancer, July 31- August 4, San Francisco (CA, USA) Prognostic and predictive Markers.

Ceppi P., Monica V., Lo Iacono M., Saviozzi S., Pautasso M., Novello S., Mussino S., Bracco E., Volante M., Papotti M., Scagliotti G.V. “Effects of Src Kinase inhibition induced by Dasatinib (BMS 354825) in the sensitivity to Cisplatin of Non-Small Cell Lung Cancer cell lines” 13th World Conference on lung cancer, July 31- August 4, San Francisco (CA, USA) Prognostic and predictive Markers.

Giaj Levra M, Pelosi E, Capelletto E, Rapetti S, Longo M, Crida B, Monica V, Novello S “Repeated ¹⁸F-FDG PET during cycle one as a predictor of early response to chemotherapy in advanced non-small cell lung cancer (NSCLC) patients (pts): preliminary results of a pilot study”. XI Congresso Nazionale AIOM 2009, 10 october 2009, Milan, Italy

Longo M, Monica V, Capelletto E, Pandiscia S, Crida B, Giaj Levra M, Rapetti SG, Novello S. “Hormonal Receptor Expression in lung cancer: a pilot study”. XI Congresso Nazionale AIOM 2009, 10 october 2009, Milan, Italy

Ghio P, Ceppi P, Giaj Levra M, Longo M, Capelletto E, Selvaggi G, Monica V, Novello S, Scagliotti GV “Circulating CD4+ CD25+ regulatory T cells (T-REGS) in patients with lung cancer (LC).” XI Congresso Nazionale AIOM 2009, 10 october 2009, Milan, Italy

Capelletto E,Sardo D, Longo M, Monica V, Giaj Levra M, Crida B, Rapetti S.G., Fava C, Novello S. “Exploratory trial evaluating the role of magnetic resonance imaging and perfusion weighted imaging in assessing the effect of Sunitinib on brain metastates (MTS) in patients (PTS) with non-small cell lung cancer (NSCLC).” XI Congresso Nazionale AIOM 2009, 10 october 2009, Milan, Italy.

V. Monica, M. Longo, S. Demichelis, B. Crida, M. Giaj Levra, S.G. Rapetti, E. Capelletto, S. Novello “Sex-linked Hormone Receptor Expression In Lung Cancer Patients: Pilot Study In A Consecutive Group Of Patients With Advanced Lung Cancer.”

Category: 09.20 - Lung Cancer: Cellular and Molecular Aspects (RCMB) Scientific Abstract

Session: C66 - MOLECULAR TARGETS FOR THERAPEUTIC DEVELOPMENT IN LUNG CANCER Session Type: Thematic Poster Session- Poster Presentation
Date: Tuesday, May 17, 2011 Abs. ID/Title: #20874. American Thoracic Society_Denver, Colorado 13-18 may 2011.

V. Monica, S. Novello, E. Bria, M. Milella, P.Visca, M. Lo Iacono, F. Cuppone, M. Longo, F. Cognetti, G. Scagliotti. “Assessment of thymidylate synthase (TS) mRNA and protein expression in non small cell lung cancer patients treated with pemetrexed-based therapies”

Poster session 2, july 5 2011. Abs. ID #1089. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

Poster session 2, july 5 2011. Abs. ID #1255. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

M. Lo Iacono, V. Monica, S. Saviozzi, P. Ceppi, E. Bracco, M. Papotti, G. Scagliotti. “Aurora Kinase A expression is associated with lung cancer histological-subtypes and with tumor de-differentiation”

Poster session 1, july 4 2011. Abs. ID #2022. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

M. Lo Iacono, V. Monica, S. Saviozzi, E. Bracco, S. Novello, M. Papotti, G. Scagliotti. “Splicing Factor hSlu7 expression in non small cell lung cancer and corresponding morphological normal lung tissue”

Poster session 1, july 4 2011. Abs. ID #2053. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

T. Vavalà, A.M. Alberti, V. Monica, M. Giaj Levra, E. Capelletto, S.G. Rapetti, M.V. Pacchiana, S. Novello “Improving Clinical Research, Resources, Support Services and Health Related Quality of Life in Age-Specific Thoracic Cancer Patients”

Poster session 4, july 7 2011. Abs. ID #754. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

S. Novello, V. Monica, M. Longo, P. Pessina, T. Vavalà, B. Felice, G. Scagliotti, M. Papotti. “Role of hormone receptor expression in patients with advanced stage lung cancer treated with chemotherapy.”

Poster session 2, july 5 2011. Abs. ID #1151. 14th World Conference on Lung Cancer (WCLC 2011) IASLC Amsterdam RAI, The Netherlands july 3-7 2011.

V. Monica, M. Lo Iacono, P. Ceppi, S. Novello, M. Volante, G. Scagliotti, M. Papotti. “IGF1R and SRC are functionally activated in non small cell lung cancer (NSCLC) and targeted by specific inhibitors” [Publication Page: P2.135]
AIOM 2011_ Bologna. Session Type: Thematic Poster Session- Poster Presentation

Silvia Novello, Christian Manegold Sr., Christian Grohe, Ida Colantonio, Monika Heidi Serke, Michael Geissler, Giuseppe Valmadre, Wolfgang Schuette, Erich Stoelben, Emilio Bria, Valentina Monica, Valter Torri, Giorgio Scagliotti. “International tailored chemotherapy adjuvant trial : Itaca trial. “ ASCO 2012_Chicago (Illinois, USA). Session Type: Poster Presentation