Supervisor

Dr. Stefano Indraccolo

Description

This research line involves the study of the genetic and molecular mechanisms underlying tumor heterogeneity and of the complex relationship between the tumor and the microenvironment, in both human tumors and preclinical models. Such research will lead to the implementation of molecular diagnostic approaches and new treatments into clinical practice, which will provide real-time benefits for cancer patients.

Background

Experimental oncology has historically been a key think tank for the conception of cancer biology models; it is also the starting point for the development of innovative cancer therapies that, over the past two decades, have become available to a wider range of cancer patients. Examples include molecular target therapies for “actionable” genes and therapies that modulate the tumor microenvironment, such as antiangiogenic therapy and immunotherapy. One of the main challenges of this research line is to combine pre-clinical observations with those obtained from clinical experience and translate this wealth of knowledge intodiagnostic and therapeutic improvements.

Rationale

One of the emerging aspects at the cross level in cancer research is the so-called tumor heterogeneity, which affects both the tumor component and the stroma, and needs to be better characterized in order to provide state of the art therapeutic options. The study of this phenomenon, with cutting-edge technologies at multiple levels (genetic, epigenetic, phenotypic), is essential for the optimization of personalized therapy with molecular target drugs, the understanding of resistance mechanisms, and for the accurate prediction of the genetic risk of cancer.

Global goals

  1. identification of new genetic alterations of pathogenetic and therapeutic relevance;
  2. characterization of tumor heterogeneity at the level of individual tumor cells;
  3. identification of metabolic and transcriptomic profiles of neoplastic cells;
  4. development of mouse models of tumor for the experimentation of innovative therapies.

Expected results

During the three-year period, completion of the IRCCS technological update and a strengthening of translational studies are expected and – starting from a better characterization of tumor biology – will lead to significant results both in terms of identification and validation of new prognostic or predictive molecular markers. Moreover, through the pre-clinical validation of new therapeutic approaches in clinically relevant mouse models, it will be possible to identify pharmacological strategies that –once transferred into the clinical setting – can lead to the improvement of current therapeutic results.

Top 15 pubblicazioni 2018 linea 1
TitoloAutoriRivistaIF grezzo
Platelet-Derived Growth Factor-D Enables Liver Myofibroblasts to Promote Tumor Lymphangiogenesis in CholangiocarcinomaCadamuro Massimiliano, Brivio Simone, Mertens Joachim, Vismara Marta, Moncsek Anja, Milani Chiara, Fingas Christian, Cristina Malerba Maria, Nardo Giorgia, Dall'Olmo Luigi, Milani Eleonora, Mariotti Valeria, Stecca Tommaso, Massani Marco, Spirli Carlo, Fiorotto Romina, Indraccolo Stefano, Strazzabosco Mario, Fabris LucaJOURNAL OF HEPATOLOGY15.04
Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers A Mendelian Randomization StudyGEMO Study Collaborators Gruppo, Qian Frank, Wang Shengfeng, Mitchell Jonathan, McGuffog Lesley, Barrowdale Daniel, Leslie Goska, Oosterwijk Jan C, Chung Wendy K, Evans D Gareth, Engel Christoph, Kast Karin, Aalfs Cora M, Adank Muriel A, Adlard Julian, Agnarsson Bjarni A, Aittom¿¿ki Kristiina, Alducci Elisa, Andrulis Irene L, Arun Banu K, Ausems Margreet G E M, Azzollini Jacopo, Barouk-Simonet Emmanuelle, Barwell Julian, Belotti Muriel, Benitez Javier, Berger Andreas, Borg Ake, Bradbury Angela R, Brunet Joan, Buys Saundra S, Caldes Trinidad, Caligo Maria A, Campbell Ian, Caputo Sandrine M, Chiquette Jocelyne, Claes Kathleen B M, Margriet Coll¿¿e J, Couch Fergus J, Coupier Isabelle, Daly Mary B, Davidson Rosemarie, Diez Orland, Domchek Susan M, Donaldson Alan, Dorfling Cecilia M, Eeles Ros, Feliubadal¿¿ Lidia, Foretova Lenka, Montagna Marco, Radice PaoloJOURNAL OF THE NATIONAL CANCER INSTITUTE11.238
Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLCMoro Massimo, Caiola Elisa, Ganzinelli Monica, Zulato Elisabetta, Rulli Eliana, Marabese Mirko, Centonze Giovanni, Busico Adele, Pastorino Ugo, de Braud Filippo G, Vernieri Claudio, Simbolo Michele, Bria Emilio, Scarpa Aldo, Indraccolo Stefano, Broggini Massimo, Sozzi Gabriella, Garassino Marina ChiaraJournal of Thoracic Oncology10.34
Genetic, epigenetic and immunologic profiling of MMR-deficient relapsed glioblastomaIndraccolo Stefano, LOMBARDI GIUSEPPE, Fassan Matteo, Pasqualini Lorenza, Giunco Silvia, Marcato Raffaella, Gasparini Alessandra, Candiotto Cinzia, Nalio Silvia, Fiduccia Pasquale, Fanelli Giuseppe Nicol¿¿, Pambuku Ardi, Della Puppa Alessandro, D'Avella Domenico, Bonaldi Laura, Gardiman Marina P, Bertorelle Roberta, De Rossi Anita, zagonel vittorinaCLINICAL CANCER RESEARCH10.199
A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer riskLu Yingchang, Beeghly-Fadiel Alicia, Wu Lang, Guo Xingyi, Li Bingshan, Schildkraut Joellen M., Im Hae Kyung, Chen Yian A., Permuth Jennifer B., Reid Brett M., Teer Jamie K., Moysich Kirsten B., Andrulis Irene L., Anton-Culver Hoda, Arun Banu K., Bandera Elisa V., Barkardottir Rosa B., Barnes Daniel R., Benitez Javier, Bjorge Line, Brenton James, Butzow Ralf, Caldes Trinidad, Caligo Maria A., Campbell Ian, Chang-Claude Jenny, Claes Kathleen B.M., Couch Fergus J., Cramer Daniel W., Daly Mary B., DeFazio Anna, Dennis Joe, Diez Orland, Domchek Susan M., D rk Thilo, Easton Douglas F., Eccles Diana M., Fasching Peter A., Fortner Ren e.T., Fountzilas George, Friedman Eitan, Ganz Patricia A., Garber Judy, Giles Graham G., Godwin Andrew K., Goldgar David E., Goodman Marc T., Greene Mark H., Gronwald Jacek, Hamann Ute, Heitz Florian, Hildebrandt Michelle A.T., H¿¿gdall Claus K., Hollestelle Antoinette, Hulick Peter J., Huntsman David G., Imyanitov Evgeny N., Isaacs Claudine, Jakubowska Anna, James Paul, Karlan Beth Y., Kelemen Linda E., Kiemeney Lambertus A., Kjaer Susanne K., Kwong Ava, Le Nhu D., Leslie Goska, Lesueur Fabienne, Levine Douglas A., Mattiello Amalia, May Taymaa, McGuffog Lesley, McNeish Iain A., Merritt Melissa A., Modugno Francesmary, Montagna Marco, Neuhausen Susan L., Nevanlinna Heli, Nielsen Finn C., Nikitina-Zake Liene, Nussbaum Robert L., Offit Kenneth, Olah Edith, Olopade Olufunmilayo I., Olson Sara H., Olsson H. kan, Osorio Ana, Park Sue K., Parsons Michael T., Peeters Petra H.M., Pejovic Tanja, Peterlongo Paolo, Phelan Catherine M., Pujana Miquel Angel, Ramus Susan J., Rennert Gad, Risch Harvey, Rodriguez Gustavo C., Rodr¿¿guez-Antona Cristina, Romieu Isabelle, Rookus Matti A., Rossing Mary Anne, Rzepecka Iwona K., Sandler Dale P., Schmutzler Rita K., Setiawan Veronica W., Sharma Priyanka, Sieh Weiva, Simard Jacques, Singer Christian F., Song Honglin, Southey Melissa C., Spurdle Amanda B., Sutphen Rebecca, Swerdlow Anthony J., Teixeira Manuel R., Teo Soo H., Thomassen Mads, Tischkowitz Marc, Toland Amanda E., Trichopoulou Antonia, Tung Nadine, Tworoger Shelley S., Van Rensburg Elizabeth J., Vanderstichele Adriaan, Vega Ana, Edwards Digna Velez, Webb Penelope M., Weitzel Jeffrey N., Wentzensen Nicolas, White Emily, Wolk Alicja, Wu Anna H., Yannoukakos Drakoulis, Zorn Kristin K., Gayther Simon A., Antoniou Antonis C., Berchuck Andrew, Goode Ellen L., Chenevix-Trench Georgia, Sellers Thomas A., Pharoah Paul D.P., Zheng Wei, Long JirongCANCER RESEARCH9.13
Human papilloma virus genotyping for the cross-sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or moreDel Mistro Annarosa, Adcock Rachael, Carozzi Francesca, Gillio-Tos Anna, De Marco Laura, Girlando Salvatore, Rizzolo Raffaella, Frayle Helena, Trevisan Morena, Sani Cristina, Burroni Elena, Giorgi Rossi Paolo, Cuzick Jack, Ronco Guglielmo, New Technologies for Cervical CancerWorking Group.INTERNATIONAL JOURNAL OF CANCER7.36
Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cellsPinazza Marica, Ghisi Margherita, Minuzzo Sonia, Agnusdei Valentina, Fossati Gianluca, Ciminale Vincenzo, Pezz¿¿ Laura, Ciribilli Yari, Pilotto Giorgia, Venturoli Carolina, Amadori Alberto, Indraccolo StefanoONCOGENE6.854
Aurora-PLK1 cascades as key signaling modules in the regulation of mitosisJoukov Vladimir, De Nicolo ArcangelaScience Signaling6.378
AKR1C enzymes sustain therapy resistance in paediatric T-ALLBortolozzi Roberta, Bresolin Silvia, Rampazzo Elena, Paganin Maddalena, Maule Francesca, Mariotto Elena, Boso Daniele, Minuzzo Sonia, Agnusdei Valentina, Viola Giampietro, Te Kronnie Geertruy, Cazzaniga Giovanni, Basso Giuseppe, Persano LucaBRITISH JOURNAL OF CANCER5.922
Selective killing of human T-ALL cells an integrated approach targeting redox homeostasis and the OMA1/OPA1 axissilic-benussi micol, Scattolin Gloria, Cavallari Ilaria, Minuzzo Sonia, Del Bianco Paola, Francescato Samuela, Basso Giuseppe, Indraccolo Stefano, D'Agostino Donna M, Ciminale VincenzoCell Death & Disease5.638
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutationsEMBRACE Gruppo, Rebbeck Timothy R, Friebel Tara M, Friedman Eitan, Hamann Ute, Huo Dezheng, Kwong Ava, Olah Edith, Olopade Olufunmilayo I, Solano Angela R, Teo Soo-Hwang, Thomassen Mads, Weitzel Jeffrey N, Chan T L, Couch Fergus J, Goldgar David E, Kruse Torben A, Palmero Edenir In¿¿z, Park Sue Kyung, Torres Diana, van Rensburg Elizabeth J, McGuffog Lesley, Parsons Michael T, Leslie Goska, Aalfs Cora M, Abugattas Julio, Adlard Julian, Agata Simona, Aittom¿¿ki Kristiina, Andrews Lesley, Andrulis Irene L, Arason Adalgeir, Arnold Norbert, Arun Banu K, Asseryanis Ella, Auerbach Leo, Azzollini Jacopo, Balma¿¿a Judith, Barile Monica, Barkardottir Rosa B, Barrowdale Daniel, Benitez Javier, Berger Andreas, Berger Raanan, Blanco Amie M, Bonanni Bernardo, Manoukian Siranoush, Montagna Marco, Radice Paolo, Tognazzo Silvia, Varesco LilianaHUMAN MUTATION5.359
The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicitykConFab/AOCS Investigators Gruppo, Colombo Mara, L¿¿pez-Perolio Irene, Meeks Huong D, Caleca Laura, Parsons Michael T, Li Hongyan, De Vecchi Giovanna, Tudini Emma, Foglia Claudia, Mondini Patrizia, Manoukian Siranoush, Behar Raquel, Garcia Encarna B G¿¿mez, Meindl Alfons, Montagna Marco, Niederacher Dieter, Schmidt Ane Y, Varesco Liliana, Wappenschmidt Barbara, Bolla Manjeet K, Dennis Joe, Michailidou Kyriaki, Wang Qin, Aittom¿¿ki Kristiina, Andrulis Irene L, Anton-Culver Hoda, Arndt Volker, Beckmann Matthias W, Beeghly-Fadel Alicia, Benitez Javier, Boeckx Bram, Bogdanova Natalia V, Bojesen Stig E, Bonanni Bernardo, Brauch Hiltrud, Brenner Hermann, Burwinkel Barbara, Chang-Claude Jenny, Conroy Don M, Couch Fergus J, Cox Angela, Cross Simon S, Czene Kamila, Devilee Peter, D¿¿rk Thilo, Eriksson Mikael, Fasching Peter A, Figueroa Jonine, Fletcher Olivia, Radice PaoloHUMAN MUTATION5.359
Accelerated aging in perinatally HIV-infected children Clinical manifestations and pathogenetic mechanismsChiappini Elena, Bianconi Martina, Dalzini Annalisa, Petrara Maria Raffaella, Galli Luisa, Giaquinto Carlo, De Rossi AnitaAging-US5.179
BCR kinase inhibitors, idelalisib and ibrutinib, are active and effective in Richter syndromeVisentin Andrea, Imbergamo Silvia, Scomazzon Edoardo, Pravato Stefano, Frezzato Federica, Bonaldi Laura, Pizzi Marco, Vio Stefania, Michele Gregianin, Burei Marta, Facco Monica, Semenzato Gianpietro, Piazza Francesco, Trentin LivioBRITISH JOURNAL OF HAEMATOLOGY5.128
In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristicsRigolin Gian Matteo, Saccenti Elena, Guardalben Emanuele, Cavallari Maurizio, Formigaro Luca, Zagatti Barbara, Visentin Andrea, Mauro Francesca R., Lista Enrico, Bassi Cristian, Lupini Laura, Quaglia Francesca Maria, Urso Antonio, Bardi Maria Antonella, Bonaldi Laura, Volta Eleonora, Tammiso Elisa, Ilari Caterina, Cafforio Luciana, Melandri Aurora, Cavazzini Francesco, Negrini Massimo, Semenzato Gianpietro, Trentin Livio, Fo¿¿ Robin, Cuneo AntonioBRITISH JOURNAL OF HAEMATOLOGY5.128

Source: IOV Scientific library