Molecular strategies to overcome cancer resistance to therapy in solid tumors
molEcular oVercome cancEr REsiStance Therapies
Prof. Laura Papucci
Brief Biographical sketch of the Coordinator
2022- today: Associate Professor at the Faculty of Medicine and Surgery disciplinary sector MED/04 – sector 06/A2 General Pathology and Clinical Pathology .2020-2024: Member of the Steering and Self-Assessment Commission of the Department of Experimental and Clinical Biomedical Sciences "Mario Serio" University of Florence2017: National Scientific Qualification for the role of Associate Professor MED/04-general Pathology (06/A2)
2016-2019 Faculty member of the Doctorate School in Biomedical Sciences (UniFI)
2012-2022 Tenure Researcher at the Department of Experimental and Clinical Biomedical Sciences (UniFI)
2005: PhD at the Doctorate School of Experimental and Clinical Oncology (UniFI). Thesis title: “Prevention of osteoclastogenesis induced by neuroblastoma cells by antisense oligonucleotides directed to RANK-L mRNA”.
1999-2007: Fellowship at the Department of Experimental Pathology and Oncology (UniFI). Research title: “Reversion of the neoplastic phenotype by modulation of the clonal survival potential by antisense oligomers”.
1999: Specialist in Biochemistry and Clinical Chemistry (UniFI). Thesis title: “Telomerase: a new method of quantitative analysis for a new tumor marker”.
1996: Fellowship from Accademia Nazionale dei Lincei at the Department of Experimental Pathology and Oncology (UniFI)
1993-1995: Fellowship from Menarini/Bristol-Myers Squibb at the Department of Experimental Pathology and Oncology (UniFI)
1993: Degree in Biological Sciences (UniFI). Thesis title: “Molecular strategies for the study of the dynamic interaction of antiblastic drugs with DNA duplication”.
Member of the following Scientific Societis
Società Italiana di Patologia e Medicina Traslazionale
Member of editorial board of the following Journals
2020: Editorial board – Biology (ISSN 2079-7737; CODEN: BBSIBX) IF. 3.796
2021: Guest Associate Editor in Gastrointestinal Cancers - Frontiers in Oncology I.F. 4.416- Special Issue: Redox Potential and Metabolic Behavior in gastrointestinal Cancer.
Dr.ssa Lucia Magnelli - Reseracher
Dr.ssa Sara Peri – pHD, Research Contract
Dr.ssa Elena Andreucci – pHD, Reserach Fellowship
Dr. Alessio Biagioni – pHD - Research Fellowship
Dr. Giampaolo Versienti – pHD student
Current and Previeus research interest
Since the beginning of my scientific activity I have been involved in the study of oncology and the process of programmed cell death in various pathologies and in particular the role of apoptosis in cancer, specifically my research has focused on the regulation of the anti-apoptotic gene bcl -2. In this sector I contributed to the development of both negative and positive regulation strategies of gene expression based on the use of antisense oligonucleotides, ribozymes and gene silencing by interfering RNAs. I also contributed to the elucidation of the post-transcriptional regulatory mechanism of the bcl-2 gene. In this context, I participated in the drafting and implementation as Senior Scientist of the projects funded by AIRC and by the Ministry of University and Research.
Always inherent in the study of the apoptotic process, I have dedicated myself to understanding the mechanisms that underlie it, both at a morphological and biochemical level, identifying a syncretic process between apoptosis and necrosis called Aponecrosis.
I have been involved for years, as a Senior Scientist, in collaborations with the surgeons of the AOUC Careggi (Professor Fabio Cianchi's team). Studies have led to clarify the proapoptotic role against colorectal cancer of some molecules such as: endocannabinoids, carbonic anhydrase inhibitors (CAIX), cox-2 inhibitors). Currently, with the surgical team with which I continue to collaborate, I am conducting studies on gastric cancer and its staging in Caucasian populations. As well as studying the underlying causes of chemoresistance and the metabolic correlations between them.
Furthermore, I am currently studying the effects of oleoeuropein and/or oleocanthal polyphenols as adjuvants of gastric cancer chemotherapy.In gastric cancer I am currently investigating the role of CAIX as an index of malignancy in its advanced stages, which is a target of particular interest for the development of new anticancer therapies through the use of CAIX inhibitors (Participant in various projects currently under evaluation including AIRC , Prin, Prin PNRR, World Wide Cancer e).CAIX and its inhibitors were also the basis of studies in collaboration with pharmacologists of the University of Florence (Professor Emanuela Masini), with whom we investigated the role of CAIX as a plasma marker of clear cell renal cell carcinoma. Always in collaboration with them, I studied the evolution towards malignancy of Barrett's esophagus pathology and the possible use of drugs suitable for its reversion.Again in the neoplastic field, in melanoma, I have been involved in the study of the various isoforms of FGF2 and how these cooperate in different stages of tumor progression, providing melanoma cells with the main malignant characteristics.Furthermore, I have recently collaborated in studies on how acidosis characterizes the microenvironment of most solid tumors and is considered a new hallmark of cancer and how the use of agents that control tumor extracellular acidosis acquires great clinical importance in the treatment of particularly aggressive tumours.I was involved in the study of the role of the TGF-beta pathway in tumor angiogenesis and its innovative inhibitors. I was involved in the study of Lipid Rafts and their role in tumor angiogenesis. I collaborated, again as Senior Scientist, with colleagues of the Department (Professor Mario del Rosso's group) in the study of the role of the urokinase-type plasminogen activator receptor (uPAR) in the regulation of the proliferation and invasiveness of tumor cells and in the angiogenesis of mature endothelial cells and endothelial progenitor cells, and how uPAR provides a regulatory mechanism in angiogenesis.For years I have collaborated in the ophthalmological field with Milanese researchers (Equipe of Professor Rosario Brancato) and, still today I collaborate with ophthalmologists of the AOUC Careggi (Professor Fabrizio Giansanti) studying the antiapoptotic effect of Coenzyme Q10 in preparations for ophthalmological use. These studies have led to the creation of a patent.Still in the ophthalmological field, I tested the toxicity of various dyes used in eye surgery at the retinal level, as well as the use of a human-mouse chimeric antibody anti-IgG inhibiting TNF-α. These studies resulted in the collaboration with Professor Indu Pal Kaur of the University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, India. The studies were aimed at the administration of drugs for ophthalmological use conveyed by nanoparticles and, currently, at the use of amniotic membranes as an aid in lesions due to retinal pathologies. In particular, studies are focusing on the development, optimization and evaluation of human amniotic membrane extract (hAME) by means of new scaffolds, for the treatment of proliferative vitroretinopathy (PVR).
Chemoresistance - Immunotherapy – Tumor molecular markers – Organoids - Trascriptomic nad proteomic profiling
Current/recent sources of funding
Faggi elargizione liberale 2020-2022
Fondi di ricerca di Ateneo
10 best pubblications of the last 5 years
Andreucci E, Biagioni A, Peri S, Versienti G, Cianchi F, Staderini F, Antonuzzo L, Supuran CT, Olivo E, Pasqualini E, Messerini L, Massi D, Lulli M, Ruzzolini J, Peppicelli S, Bianchini F, Schiavone N, Calorini L, Magnelli L, Papucci L. The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs. Cancer Lett. 2023 Sep 1;571:216338. doi: 10.1016/j.canlet.2023.216338. Epub 2023 Aug 6. PMID: 37549770.
Peri S, Ruzzolini J, Urciuoli S, Versienti G, Biagioni A, Andreucci E, Peppicelli S, Bianchini F, Bottari A, Calorini L, Nediani C, Magnelli L, Papucci L. An Oleocanthal-Enriched EVO Oil Extract Induces the ROS Production in Gastric Cancer Cells and Potentiates the Effect of Chemotherapy. Antioxidants (Basel). 2022 Sep 7;11(9):1762. doi: 10.3390/antiox11091762. PMID: 36139836; PMCID: PMC9495378.
Peri S, Biagioni A, Versienti G, Andreucci E, Staderini F, Barbato G, Giovannelli L, Coratti F, Schiavone N, Cianchi F, Papucci L, Magnelli L. Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line. Int J Mol Sci. 2021 Jul 19;22(14):7698. doi: 10.3390/ijms22147698. PMID: 34299320; PMCID: PMC8303918.
Singh M, Schiavone N, Papucci L, Maan P, Kaur J, Singh G, Nandi U, Nosi D, Tani A, Khuller GK, Priya M, Singh R, Kaur IP. Streptomycin sulphate loaded solid lipid nanoparticles show enhanced uptake in macrophage, lower MIC in Mycobacterium and improved oral bioavailability. Eur J Pharm Biopharm. 2021 Mar;160:100-124. doi: 10.1016/j.ejpb.2021.01.009. Epub 2021 Jan 23. PMID: 33497794.
Andreucci E, Peppicelli S, Ruzzolini J, Bianchini F, Biagioni A, Papucci L, Magnelli L, Mazzanti B, Stecca B, Calorini L. The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells. J Mol Med (Berl). 2020 Oct;98(10):1431-1446. doi: 10.1007/s00109-020-01959-y. Epub 2020 Aug 15. PMID: 32803272; PMCID: PMC7525286.
Magnelli L, Schiavone N, Staderini F, Biagioni A, Papucci L. MAP Kinases Pathways in Gastric Cancer. Int J Mol Sci. 2020 Apr 21;21(8):2893. doi: 10.3390/ijms21082893. PMID: 32326163; PMCID: PMC7215608.
Lulli M, Nencioni D, Papucci L, Schiavone N. Zeta-crystallin: a moonlighting player in cancer. Cell Mol Life Sci. 2020 Mar;77(6):965-976. doi: 10.1007/s00018-019-03301-3. Epub 2019 Sep 28. PMID: 31563996.
Biagioni A, Skalamera I, Peri S, Schiavone N, Cianchi F, Giommoni E, Magnelli L, Papucci L. Update on gastric cancer treatments and gene therapies. Cancer Metastasis Rev. 2019 Sep 5. doi: 10.1007/s10555-019-09803-7. Review.
Lucarini L, Magnelli L, Schiavone N, Crisci A, Innocenti A, Puccetti L, Cianchi F, Peri S, Supuran CT, Papucci L, Masini E. Plasmatic carbonic anhydrase IX as a diagnostic marker for clear cell renal cell carcinoma. J Enzyme Inhib Med Chem. 2018 Dec;33(1):234-240.
Lucarini L, Magnelli L, Schiavone N, Crisci A, Innocenti A, Puccetti L, Cianchi F, Peri S, Supuran CT, Papucci L, Masini E. Plasmatic carbonic anhydrase IX as a diagnostic marker for clear cell renal cell carcinoma. J Enzyme Inhib Med Chem. 2018 Dec;33(1):234-240. doi: 10.1080/14756366.2017.1411350. PMID: 29251173; PMCID: PMC7011953.
Prof. Fabio Cianchi – Direttore del Centro Interdipartimentale Per Lo Sviluppo Di Nuove Tecnologie Mini-Invasive In Chirurgia Oncologica (C.O.M.I.S) – Afferente al Dipartimento di Medicina Sperimentale - Università di Firenze
Prof. Claudiu Trandafir Supuran - Dipartimento di Neuroscienze, Area Del Farmaco E Salute Del Bambino (Neurofarba)
Prof. Lorenzo Antonuzzo - Dipartimento di Medicina Sperimentale e Clinica
Prof. Fabrizio Giansanti - Dipartimento di Neuroscienze, Area Del Farmaco E Salute Del Bambino (Neurofarba)
Prof. Indu Pal Kaur - Chairperson, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Sector-14, Chandigarh, India
Prof. L. Papucci- Dr. Lucia Magnelli