Experimental Therapeutics

Members

.Carlo Catapano, MD PhD, Group Leader
Aleksandra Kokanovic, Research Assistant
Alessio Fusina, MS student
Elisa Sorrenti, MS student
Enrica Mira Catò
Gianluca Civenni, PhD
Jessica Merulla, PhD
Martina Giurdanella, MS student
Ramiro Vazquez, PhD

Overview

Current objectives of the research in my group are the investigation of transcriptional and epigenetic mechanisms in human cancers and the development of innovative therapeutic strategies. Transcription factors are central nodes in multiple oncogenic pathways and represent attractive targets for development of new cancer therapeutics. However, very few direct pharmacological inhibitors of transcription factors are currently available. My group is investigating various approaches, including small molecule inhibitors, small interfering RNAs and oligonucleotides, to block the activity of oncogenic transcription factors. Furthermore, extensive modifications of the epigenetic landscape occur along with deregulated activity of transcription factors and are at the basis of the phenotypic reprogramming associated with tumor development, progression and treatment resistance. We are investigating the role of epigenetic regulators in tumor progression and treatment resistance and the impact of specific inhibitors on these processes. Novel epigenetic effectors, such as promoter-associated long noncoding RNAs, microRNAs and RNA binding proteins, are also investigated as potential targets for innovative therapeutic strategies. Ultimately, stem-like tumor cells in human tumors are emerging as important players in tumor progression, metastasis and treatment failure. It is therefore becoming apparent that it is necessary to block the cancer stem-like cell subpopulation in order to have an effective and lasting impact of the disease. With this intent we are exploring the biological pathways responsible for self-renewal, expansion and maintenance of stem-like tumor cells in human cancers. A major focus is on the processes that underlie the epigenetic and metabolic reprogramming and sustain the stem-like phenotype. In collaboration with the prostate cancer biology group at the IOR, we have established protocols and experimental models to study cancer cells with stem-like features in vitro and in vivo. These systems are used to study the specific features of cancer stem cells and test inhibitors of key pathways to establish their potential for therapeutic applications.

Current projects

  • Targeting metabolic reprogramming and plasticity of cancer stem cells to impact on tumor progression and treatment resistance
  • Novel therapeutic strategies to prevent disease progression in ERG fusion positive prostate cancer
  • Promoter proximal long noncoding RNA and epigenetic regulatory networks in human cancer
  • Targeting Lin28-dependent cancers
  • Structural basis for the inhibition of STAT3 transcription factor by small molecules
  • Biological and genetic determinants of response to transcriptional inhibitors in human cancers
  • Novel epigenetic targets for cancer therapy

Recent publications

  • Civenni G, Albino D, Shinde D, Vázquez R, Merulla J, Kokanovic A, Mapelli SN, Carbone GM, Catapano Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells. Front Oncol. 2019 May 9;9:385. doi: 10.3389/fonc.2019.00385.
  • Civenni G, Bosotti R, Timpanaro A, Vàzquez R, Merulla J, Pandit S, Rossi S, Albino D, Allegrini S, Mitra A, Mapelli SN, Vierling L, Giurdanella M, Marchetti M, Paganoni A, Rinaldi A, Losa M, Mira-Catò E, D’Antuono R, Morone D, Rezai K, D’Ambrosio G, Ouafik L, Mackenzie S, Riveiro ME, Cvitkovic E, Carbone GM, Catapano Epigenetic control of mitochondrial fission enables self-renewal of stem-like tumor cells in human prostate cancer. Cell Metab. 2019 May 20. doi:10.1016/j.cmet.2019.05.004.
  • Mapelli, S.N., Napoli, S., Pisignano, G., Garcia-Escudero, R., Carbone, G.M., and Catapano, C.V. Deciphering the complexity of human noncoding promoter-proximal transcriptome. Bioinformatics. 2018 Dec 10. doi: 10.1093/bioinformatics/bty981.
  • Shinde D, Albino D, Zoma M, Mutti A, Mapelli SN, Civenni G, Kokanovic A, Merulla J, Perez-Escudero J, Costales P, Moris F, Catapano CV, Carbone GM. Transcriptional Reprogramming and Inhibition of Tumor-propagating Stem-like Cells by EC-8042 in ERG-positive Prostate Cancer. Eur Urol Oncol 2018org/10.1016/j.euo.2018.08.024.
  • Scimeca M, Urbano N, Bonfiglio R, Mapelli SN, Catapano CV, Carbone GM, Ciuffa S, Tavolozza M, Schillaci O, Mauriello A, Bonanno E. Prostate Osteoblast-Like Cells: A Reliable Prognostic Marker of Bone Metastasis in Prostate Cancer Patients. Contrast Media Mol Imaging. 2018 Dec 9;2018:9840962. doi: 10.1155/2018/9840962.
  • Civenni G, Carbone GM, Catapano Overview of Genetically Engineered Mouse Models of Prostate Cancer and Their Applications in Drug Discovery. Curr Protoc Pharmacol. 2018 Jun;81(1):e39. doi: 10.1002/cpph.39.
  • Sgrignani J, Garofalo M, Matkovic M, Merulla J, Catapano CV, Cavalli A. Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development. Int J Mol Sci. 2018 May 28;19(6). pii: E1591. doi:10.3390/ijms19061591. Review. PubMed PMID: 29843450; PubMed Central PMCID: PMC6032208.
  • Pisignano G, Napoli S, Magistri M, Mapelli SN, Pastori C, Di Marco S, Civenni G, Albino D, Enriquez C, Allegrini S, Mitra A, D’Ambrosio G, Mello-Grand M,Chiorino G, Garcia-Escudero R, Varani G, Carbone GM, Catapano A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers. Nat Commun. 2017 May 30;8:15622.
  • Genini D, Brambilla L, Laurini E, Merulla J, Civenni G, Pandit S, D’Antuono R,Perez L, Levy DE, Pricl S, Carbone GM, Catapano Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4924-E4933.
  • Napoli S, Piccinelli V, Mapelli S, Pisignano G, Catapano Natural antisense transcripts drive a regulatory cascade controlling c-MYC transcription. RNA Biol. 2017 Aug 14:0. doi: 10.1080/15476286.2017.1356564.

Catapano – Complete Publication List