Maurizio Scaltriti
I lead a team of translational scientists who work on projects in our tumour drivers and resistance, DNA damage response and epigenetics portfolio. We study tumour biology, drive innovation in clinical trial design and accelerate clinical decision making with cutting-edge technologies.
Before joining AstraZeneca in October 2020, I was an Associate Professor and the Associate Director of Translational Science at Memorial Sloan Kettering Cancer Center. In this role I worked closely with early drug development physicians – enabling new findings and hypotheses from the clinic to be quickly evaluated in the laboratory setting.
My research interests have been focused on elucidating tumour vulnerabilities to improve patient selection and how the selective pressure imposed by targeted therapy impacts drug resistance. Highlights from my early research include the identification of resistance mechanisms to PI3K inhibitors and to anti-HER2 therapy. I also worked on the characterisation of actionable genomic alterations found in solid tumours that prompted the testing of novel therapeutic strategies.
In my team at AstraZeneca, we provide the scientific rationale for the design of novel combinatorial strategies and identify biomarkers of response to therapy. We are focused on strategies for assets in our tumour drivers and resistance, DNA damage response and epigenetics scientific platforms.
I am passionate about bridging the gap between the clinic and the laboratory to bring new treatment options to patients with cancer
2015
2014
2010
CURRENT ROLE
2020
2016
2013
Career highlights
2015
2009, 2015
2009, 2015
Featured publications
Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer
Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon y Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007 Apr 18;99(8):628-38. doi: 10.1093/jnci/djk134
Link: http://pubmed.ncbi.nlm.nih.gov/17440164/
Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity
Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K, Smith DJ, Landolfi S, Ramon y Cajal S, Arribas J, Baselga J. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene. 2009 Feb 12;28(6):803-14. doi: 10.1038/onc.2008.432. Epub 2008 Dec 8.
Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor
Scaltriti M, Chandarlapaty S, Prudkin L, Aura C, Jimenez J, Angelini PD, Sánchez G, Guzman M, Parra JL, Ellis C, Gagnon R, Koehler M, Gomez H, Geyer C, Cameron D, Arribas J, Rosen N, Baselga J. Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor. Clin Cancer Res. 2010 May 1;16(9):2688-95. doi: 10.1158/1078-0432.CCR-09-3407. Epub 2010 Apr 20.
HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers
Li BT, Michelini F, Misale S, Cocco E, Baldino L, Cai Y, Shifman S, Tu HY, Myers ML, Xu C, Mattar M, Khodos I, Little M, Qeriqi B, Weitsman G, Wilhem CJ, Lalani AS, Diala I, Freedman RA, Lin NU, Solit DB, Berger MF, Barber PR, Ng T, Offin M, Isbell JM, Jones DR, Yu HA, Thyparambil S, Liao WL, Bhalkikar A, Cecchi F, Hyman DM, Lewis JS, Buonocore DJ, Ho AL, Makker V, Reis-Filho JS, Razavi P, Arcila ME, Kris MG, Poirier JT, Shen R, Tsurutani J, Ulaner GA, de Stanchina E, Rosen N, Rudin CM, Scaltriti M. HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers. Cancer Discov. 2020 May;10(5):674-687. doi: 10.1158/2159-8290.CD-20-0215. Epub 2020 Mar 25
Link: http://pubmed.ncbi.nlm.nih.gov/32213539/
Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor
Juric D, Castel P, Griffith M, Griffith OL, Won HH, Ellis H, Ebbesen SH, Ainscough BJ, Ramu A, Iyer G, Shah RH, Huynh T, Mino-Kenudson M, Sgroi D, Isakoff S, Thabet A, Elamine L, Solit DB, Lowe SW, Quadt C, Peters M, Derti A, Schegel R, Huang A, Mardis ER, Berger MF, Baselga J, Scaltriti M. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature. 2015 Feb 12;518(7538):240-4. doi: 10.1038/nature13948. Epub 2014 Nov 17.
Link: http://pubmed.ncbi.nlm.nih.gov/25409150/
PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kα Inhibition
Castel P, Ellis H, Bago R, Toska E, Razavi P, Carmona FJ, Kannan S, Verma CS, Dickler M, Chandarlapaty S, Brogi E, Alessi DR, Baselga J, Scaltriti M. PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kα Inhibition. Cancer Cell. 2016 Aug 8;30(2):229-242. doi: 10.1016/j.ccell.2016.06.004. Epub 2016 Jul 21.
Link: http://pubmed.ncbi.nlm.nih.gov/27451907/
PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer
Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med. 2015 Apr 15;7(283):283ra51. doi: 10.1126/scitranslmed.aaa4442. Erratum in: Sci Transl Med. 2018 Oct 24;10(464)
Link: http://pubmed.ncbi.nlm.nih.gov/25877889/
FOXA1 Mutations Reveal Distinct Chromatin Profiles and Influence Therapeutic Response in Breast Cancer
Arruabarrena-Aristorena A, Maag JLV, Kittane S, Cai Y, Karthaus WR, Ladewig E, Park J, Kannan S, Ferrando L, Cocco E, Ho SY, Tan DS, Sallaku M, Wu F, Acevedo B, Selenica P, Ross DS, Witkin M, Sawyers CL, Reis-Filho JS, Verma CS, Jauch R, Koche R, Baselga J, Razavi P, Toska E, Scaltriti M. FOXA1 Mutations Reveal Distinct Chromatin Profiles and Influence Therapeutic Response in Breast Cancer. Cancer Cell. 2020 Oct 12;38(4):534-550.e9. doi: 10.1016/j.ccell.2020.08.003. Epub 2020 Sep 3.
Link: http://pubmed.ncbi.nlm.nih.gov/32888433/
Resistance to TRK inhibition mediated by convergent MAPK pathway activation
Cocco E, Schram AM, Kulick A, Misale S, Won HH, Yaeger R, Razavi P, Ptashkin R, Hechtman JF, Toska E, Cownie J, Somwar R, Shifman S, Mattar M, Selçuklu SD, Samoila A, Guzman S, Tuch BB, Ebata K, de Stanchina E, Nagy RJ, Lanman RB, Houck-Loomis B, Patel JA, Berger MF, Ladanyi M, Hyman DM, Drilon A, Scaltriti M. Resistance to TRK inhibition mediated by convergent MAPK pathway activation. Nat Med. 2019 Sep;25(9):1422-1427. doi: 10.1038/s41591-019-0542-z. Epub 2019 Aug 12.
Link: http://pubmed.ncbi.nlm.nih.gov/31406350/
TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors.
Cocco E, Lee JE, Kannan S, Schram AM, Won HH, Shifman S, Kulick A, Baldino L, Toska E, Arruabarrena-Aristorena A, Kittane S, Wu F, Cai Y, Arena S, Mussolin B, Kannan R, Vasan N, Gorelick AN, Berger MF, Novoplansky O, Jagadeeshan S, Liao Y, Rix U, Misale S, Taylor BS, Bardelli A, Hechtman JF, Hyman DM, Elkabets M, de Stanchina E, Verma CS, Ventura A, Drilon A, Scaltriti M. TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors. Cancer Discov. 2021 Jan;11(1):126-141. doi: 10.1158/2159-8290.CD-20-0571. Epub 2020 Oct 1.
Link: http://pubmed.ncbi.nlm.nih.gov/33004339/
Veeva ID: Z4-45787
Date of preparation: June 2022