ONCOLOGY AREA

(Prof. Lucia Altucci, Prof. Michele Caraglia)

Oncology and Precision Medicine (Prof. Michele Caraglia)

The Molecular and Precision Oncology laboratory, coordinated by Prof. Michele Caraglia and managed by Dr. Marianna Scrima, focuses on the characterization of circulating miRNA signatures, with the aim of proposing new diagnostic and therapeutic approaches. The main goal is to determine a circulating miRNA signature with innovative nanosensors, for the diagnostic and prognostic determination of squamous cell carcinoma of the larynx and more generally of the tumors of the head and neck area. This new technology will be applicable for any other neoplasia of which there are known circulating miRNA signatures to be determined in real time in the patients' blood through a nanotechnological device easy-to-use directly at the point of care (i.e., the patient's bed), without the need for complicated laboratory procedures. The biological role of these miRNAs in human cancers is also studied in order to identify new therapeutic strategies, based on the regulation of miRNA expression in cancer cells, through the use of nanotechnological approaches. The laboratory is also able to perform genotypic characterization in next generation sequencing (NGS) of human cancers, such as colorectal, breast, bladder, lung and hepatocellular carcinoma. These molecular features are useful for understanding the biological mechanisms that guide their development and determine their response to treatments.

The laboratory is also working to the characterization of gene expression of individual tumor cells, through single cell (nuclei) RNA sequencing techniques (with reference to squamous cell tumors of the head and neck district), and to the determination of the prognostic and predictive impact of responses of individual cellular genetic signatures. This project will allow us to identify new tumor-specific markers that can be useful for diagnostic and prognostic definition and for the identification of the component in the tumor microenvironment that influences the clinical course of the neoplasm. This information is important also for predicting the response of patients to immunotherapy and for identifying new therapeutic targets. These studies are supported by the characterization of the gene expression of the neoplasm from paraffin-embedded tissues of the same patients and of a cohort of patients along with all the clinical and pathological information. (Dr. Federica Melisi, Dr. Alessia Maria Cossu, Dr. Marco Bocchetti).

Another project is currently in progress, in collaboration with the Biogem Computational Biology laboratory. This project aims to identify the fragmented circulating tumor DNA and the methylation of regions of circulating tumor DNA from plasma of patients affected by various neoplasms (colon, breast, melanoma, lung, head and neck tumors, bladder) in order to determine signatures capable of early diagnosis of cancer and of predicting survival and response to treatments. The design of a bioinformatics algorithm will make possible to predict the presence of the neoplasm, the primary tissue of origin and the prognostic characteristics.

Finally, in collaboration with the Biogem Translational Nephrology laboratory, there is a project in progress about the characterization of circulating miRNAs in the serum of renal transplant patients who develop post-transplant neoplasms, with the aim of identifying a predictive signature (Dr. Piera Grisolia, Dr. Cinzia Graziano, Dr. Clara Iannarone).

Other projects presently in progress:

  • Study of the effects of hypoxia on the genotypic and epigenetic characteristics of human mesothelioma (Dr. Marco Bocchetti, Dr. Cinzia Graziano).
  • Genotypic characterization of thin melanoma: impact on prognosis and response prediction (Dr. Federica Melisi, Dr. Lucia Pasquale).
  • Study of the cross-talk between micro-RNA and long non coding RNA in human hepatocellular carcinoma (Dr. Marco Bocchetti).
  • Characterization of the effects of radiotherapy on gene expression in glioblastoma cells (Dr. Federica Melisi, Dr. Lucia Pasquale).
  • Study of the genetic susceptibility to neoplastic cachexia (Dr. Lucia Pasquale).
  • Study of genetic and epigenetic susceptibility to SARS-Cov-2 infection (Dr. Alessia Maria Cossu, Dr. Clara Iannarone).

Technologies used / developed

The Molecular and Precision Oncology laboratory is equipped with technology for molecular and cell biology. In particular, it has clean rooms for cell cultures with safety devices for the manipulation of viral strains; a confocal microscope in white light and fluorescence, equipped with a CCD camera, FACS; equipment for gene sequencing of Next Generation Sequencing (PGM, Ion GeneStudio™ S5 System, Illumina Next 550), QuantStudio 7 Flex Real-Time; RT-PCR equipment (Pyromax and Therascreen); FACS cell sorter BD for the isolation and collection of single cells, based on their phenotypic characteristics.

Services offered

The laboratory aims to offer the genotypic characterization of colorectal and breast carcinomas of samples from patients affected by these diseases, in order to develop a collaborative network between the main universities and hospitals in Campania region. Thanks to a bioinformatics tool that optimizes and simplifies the annotation of sequence data, the analysis obtained by evaluating quality score and frequency parameters would allow for the development of a personalized medicine. In this way, therapeutic treatments could be developed based on the characteristics of each patient, with the right combination of drugs (based on each patient’s genetic profile and the profile of the disease) with the appropriate dose and at the right time.

Epigenetica

(Prof.ssa Lucia Altucci e Prof. Vincenzo Carafa)

The medical epigenetics group studies the role of epigenomic alterations and epigenetic modifications, also at the single cell level, in human pathologies, with a focus on leukemia and solid tumors, degenerative, cardiovascular and metabolic pathologies. The identification of epigenetic biomarkers allows for the development new therapeutic targets and diagnostic and prognostic targets. Our group aims at translational activities, including the identification and characterization of epimutations, and the development of diagnostic and prognostic methods for identifying the disease and the response to treatments. The group also focuses on drug discovery activities, to identify and characterize innovative treatments based on the use of new molecules that target chromatin.

SPECIFIC LINES OF RESEARCH

  1. Characterization of the role of sirtuins (and modulators) in human development and pathologies.
  2. Identification and characterization of the role of class B acetyltransferases in tumors.
  3. Characterization of epigenomic alterations in leukemias with bioinformatics methods
  4. Characterization of epigenomic alterations in colorectal cancer, with bioinformatics methods
  5. Identification and characterization of the role of micro-vesicles in cell communication and in human pathologies, such as tumors.
  6. Use of alterations in metabolic pathways for the development of innovative therapeutic strategies.
  7. Innovative epigenetic approaches for the identification of therapeutic strategies against SARS-Cov-2.

Latest publications with first, last, and/or corresponding author

 

2023

1.     Martino S, Tammaro C, Misso G, Falco M, Scrima M, Bocchetti M, Rea I, De Stefano L, Caraglia M. microRNA Detection via Nanostructured Biochips for Early Cancer Diagnostics. Int J Mol Sci. 2023 Apr 24;24(9):7762. doi: 10.3390/ijms24097762. 

2.     Bocchetti M, Ferraro MG, Melisi F, Grisolia P, Scrima M, Cossu AM, Yau TO. Overview of current detection methods and microRNA potential in Clostridioides difficile infection screening. World J Gastroenterol. 2023 Jun 14;29(22):3385-3399. doi: 10.3748/wjg.v29.i22.3385.

2024

1.     Luce A, Abate M, Scognamiglio G, Montella M, Iervolino D, Campione S, Di Mauro A, Sepe O, Gigantino V, Tathode MS, Ferrara G, Monaco R, De Dominicis G, Misso G, Gentile V, Franco R, Zappavigna S, Caraglia M. Immune cell infiltration and inflammatory landscape in primary brain tumours. J Transl Med. 2024 May 30;22(1):521. doi: 10.1186/s12967-024-05309-1. 

2.     Cossu AM, Melisi F, Noviello TMR, Pasquale LS, Grisolia P, Reale C, Bocchetti M, Falco M, Tammaro C, Accardo N, Longo F, Allosso S, Mesolella M, Addeo R, Perri F, Ottaiano A, Ricciardiello F, Amler E, Ambrosino C, Misso G, Ceccarelli M, Caraglia M, Scrima M. MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer. Mol Ther Nucleic Acids. 2024 Feb 6;35(1):102140. doi: 10.1016/j.omtn.2024.102140.

3.     Bocchetti M, Luce A, Iannarone C, Pasquale LS, Falco M, Tammaro C, Abate M, Ferraro MG, Addeo R, Ricciardiello F, Motta G, De Stefano L, Caraglia F, Ceccarelli A, Zappavigna S, Scrima M, Cossu AM, Caraglia M, Misso G. Exosomes multiplex profiling, a promising strategy for early diagnosis of laryngeal cancer. J Transl Med. 2024 Jun 20;22(1):582. doi: 10.1186/s12967-024-05396-0. 

4.     Ottaiano A, Santorsola M, Ianniello M, Ceccarelli A, Casillo M, Sabbatino F, Petrillo N, Cascella M, Caraglia F, Picone C, Perri F, Sirica R, Zappavigna S, Nasti G, Savarese G, Caraglia M. Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment. J Transl Med. 2024 Apr 22;22(1):379. doi: 10.1186/s12967-024-05184-w. 

5.     Bocchetti M, Misso G, Zappavigna S, Scrima M, Caraglia M, Pentimalli F, Cossu AM. Advancing prognostic understanding in hepatocellular carcinoma through the integration of genomic instability and lncRNA signatures: GILncSig model. World J Gastrointest Surg. 2024 Sep 27;16(9):2774-2777. doi: 10.4240/wjgs.v16.i9.2774.

6.     Falco M, Tammaro C, Cossu AM, Takeuchi T, Tufano R, Ceccarelli M, Scafuro G, Zappavigna S, Grimaldi A, Scrima M, Ottaiano A, Savarese G, Fico A, Mesolella M, Fasano M, Motta G, Massimilla EA, Addeo R, Ricciardiello F, Caraglia M, Misso G. Identification and bioinformatic characterization of a serum miRNA signature for early detection of laryngeal squamous cell carcinoma. J Transl Med. 2024 Jul 10;22(1):647. doi: 10.1186/s12967-024-05385-3.

7.     Grisolia P, Tufano R, Iannarone C, De Falco A, Carlino F, Graziano C, Addeo R, Scrima M, Caraglia F, Ceccarelli A, Nuzzo PV, Cossu AM, Forte S, Giuffrida R, Orditura M, Caraglia M, Ceccarelli M. Differential methylation of circulating free DNA assessed through cfMeDiP as a new tool for breast cancer diagnosis and detection of BRCA1/2 mutation. J Transl Med. 2024 Oct 15;22(1):938. doi: 10.1186/s12967-024-05734-2.

8.     Abate M, Porru M, Campani V, Leonetti C, Nele V, Di Paola R, De Martino M, Russo M, Tathode M, Cossu AM, Bocchetti M, Angelillo A, Ianniello M, Petrillo N, Savarese G, Monica RD, Chiariotti L, Addeo R, Caraglia M, De Rosa G, Zappavigna S. Self-assembling nanoparticles for delivery of miR-603 and miR-221 in glioblastoma as a new strategy to overcome resistance to temozolomide. J Control Release. 2025 Jan 10;377:458-469. doi: 10.1016/j.jconrel.2024.11.039. 

9.     Di Mauro A, Santorsola M, Savarese G, Sirica R, Ianniello M, Cossu AM, Ceccarelli A, Sabbatino F, Bocchetti M, Carratù AC, Pentimalli F, Ferrara G, Nasti G, Caraglia M, Ottaiano A. High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients. J Transl Med. 2024 Dec 5;22(1):1107. doi: 10.1186/s12967-024-05927-9. Erratum in: J Transl Med. 2025 Jan 8;23(1):28. doi: 10.1186/s12967-024-05971-5. 

2025

1.     Martino S, Yilmaz D, Tammaro C, Misso G, Esposito A, Falco M, Cossu AM, Lombardi A, Amler E, Divin R, Giannetti A, Scrima M, Dardano P, De Stefano L, Rea I, De Luca AC, Caraglia M. Flexible 3D nanofiber-based SERS biosensor for detection of miRNA-223-3p in early Laryngeal Cancer diagnosis. Talanta. 2025 Apr 1;285:127293. doi: 10.1016/j.talanta.2024.127293. 

2.     Abate M, Porru M, Campani V, Leonetti C, Nele V, Di Paola R, De Martino M, Russo M, Tathode M, Cossu AM, Bocchetti M, Angelillo A, Ianniello M, Petrillo N, Savarese G, Monica RD, Chiariotti L, Addeo R, Caraglia M, De Rosa G, Zappavigna S. Self-assembling nanoparticles for delivery of miR-603 and miR-221 in glioblastoma as a new strategy to overcome resistance to temozolomide. J Control Release. 2025 Jan 10;377:458-469. doi: 10.1016/j.jconrel.2024.11.039. 

3.     Simeoni M, Tufano R, Grandinetti V, Cossu AM, Alfieri C, Pollastro R, Calcutta A, Scrima M, Bocchetti M, Zappavigna S, Simeone I, Grandaliano G, Capasso A, Messa P, Castellano G, Mella A, Biancone L, Ceccarelli M, Caraglia M, La Manna G, Capasso G, Citterio F. MicroRNA signatures of cancer risk in kidney transplant patients: insights from the COMETA study. J Transl Med. 2025 Oct 3;23(1):1053. doi: 10.1186/s12967-025-07030-z.

4.     Ianniello M, Ottaiano A, Bocchetti M, Ruggiero R, Santorsola M, Sirica R, Caraglia F, Ceccarelli A, Toscano E, Picone C, Ciappina G, Cossu AM, Petrillo N, Fico A, Circelli L, Sabbatino F, Barone A, Sperlongano R, Berretta M, Caraglia M, Savarese G. Tumor mutational burden modulates the prognostic effect of RAS mutations in metastatic colon cancer: mechanistic insights and genotype-phenotype correlations. J Transl Med. 2025 Nov 5;23(1):1226. doi: 10.1186/s12967-025-07273-w. 

5.     Cossu AM, Pace S, Bruno F, Abbatiello L, Cerchia C, Falbo E, Muñoz Ramírez AC, Kretzer C, Miek L, Troisi F, Gerstmeier J, Ambrosino P, Zappavigna S, La Vecchia A, Werz O, Caraglia M, Filosa R. Evaluation of molecular mechanisms of (Z)-3-(pentadec-10'-enyl)-catechol (litreol) and synthetic derivatives as inhibitors of human leukotriene biosynthesis. Redox Biol. 2025 Nov;87:103880. doi: 10.1016/j.redox.2025.103880.

6.     Caputo C, Lombardi A, Vicario M, Cautela D, Addeo R, Melisi F, Grimaldi A, Necas A, Amler E, Sperlongano R, Caraglia M. Early phase development of PI3kinase inhibitors for anticancer therapies. Expert Opin Investig Drugs. 2025 Nov;34(11):905-920. doi: 10.1080/13543784.2025.2582080. 

7.     Capuozzo M, Picone C, Sabbatino F, Santorsola M, Caraglia F, Iervolino D, Sirica R, Gualillo O, Di Mauro G, Castiello R, Ianniello M, Cossu AM, Nebbioso A, Altucci L, Izzo F, Patrone R, Belli A, Berretta M, Cascella M, Perri F, Carratù AC, Nasti G, Di Maio M, Giordano A, Savarese G, Caraglia M, Ottaiano A. Genetic, Epidemiological, Clinical, and Therapeutic Trajectories in Colon and Rectal Cancers. Cancers (Basel). 2025 Oct 27;17(21):3438. doi: 10.3390/cancers17213438. 

EPIGENETIC

2023

1.     Chianese U, Papulino C, Ali A, Ciardiello F, Cappabianca S, Altucci L, Carafa V, Benedetti R. FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma. J Transl Med. 2023 Jan 17;21(1):32. doi: 10.1186/s12967-023-03874-5. 

2.     Capone V, Della Torre L, Carannante D, Babaei M, Altucci L, Benedetti R, Carafa V. HAT1: Landscape of Biological Function and Role in Cancer. Cells. 2023 Apr 2;12(7):1075. doi: 10.3390/cells12071075. 

3.     Montella L, Cuomo M, Del Gaudio N, Buonaiuto M, Costabile D, Visconti R, Di Risi T, Vinciguerra R, Trio F, Ferraro S, Bove G, Facchini G, Altucci L, Chiariotti L, Della Monica R. Epigenetic alterations in glioblastomas: Diagnostic, prognostic and therapeutic relevance. Int J Cancer. 2023 Aug 1;153(3):476-488. doi: 10.1002/ijc.34381. 

4.     Bove G, Amin S, Babaei M, Benedetti R, Nebbioso A, Altucci L, Del Gaudio N. Interplay between m6 A epitranscriptome and epigenome in cancer: current knowledge and therapeutic perspectives. Int J Cancer. 2023 Aug 1;153(3):464-475. doi: 10.1002/ijc.34378.

5.     Chianese U, Papulino C, Megchelenbrink W, Tambaro FP, Ciardiello F, Benedetti R, Altucci L. Epigenomic machinery regulating pediatric AML: Clonal expansion mechanisms, therapies, and future perspectives. Semin Cancer Biol. 2023 Jul;92:84-101. doi: 10.1016/j.semcancer.2023.03.009. 

6.     Varghese B, Chianese U, Capasso L, Sian V, Bontempo P, Conte M, Benedetti R, Altucci L, Carafa V, Nebbioso A. SIRT1 activation promotes energy homeostasis and reprograms liver cancer metabolism. J Transl Med. 2023 Sep 15;21(1):627. doi: 10.1186/s12967-023-04440-9. 

7.     Sgueglia G, Longobardi S, Valerio D, Campitiello MR, Colacurci N, Di Pietro C, Battaglia R, D'Hooghe T, Altucci L, Dell'Aversana C. The impact of epigenetic landscape on ovarian cells in infertile older women undergoing IVF procedures. Clin Epigenetics. 2023 May 4;15(1):76. doi: 10.1186/s13148-023-01490-0.

8.     Conte M, Di Mauro A, Capasso L, Montella L, De Simone M, Nebbioso A, Altucci L. Targeting HDAC2-Mediated Immune Regulation to Overcome Therapeutic Resistance in Mutant Colorectal Cancer. Cancers (Basel). 2023 Mar 24;15(7):1960. doi: 10.3390/cancers15071960. 

2024

1.     Bove G, Del Gaudio N, Altucci L. Epitranscriptomics and epigenetics: two sides of the same coin? Clin Epigenetics. 2024 Sep 3;16(1):121. doi: 10.1186/s13148-024-01729-4.

2.     Della Torre L, Beato A, Capone V, Carannante D, Verrilli G, Favale G, Del Gaudio N, Megchelenbrink WL, Benedetti R, Altucci L, Carafa V. Involvement of regulated cell deaths in aging and age-related pathologies. Ageing Res Rev. 2024 Mar;95:102251. doi: 10.1016/j.arr.2024.102251. 

3.     Papulino C, Benedetti R, Altucci L. Harnessing normalcy: The potential of healthy tissue for patient outcomes. Int J Cancer. 2024 Nov 1;155(9):1531-1532. doi: 10.1002/ijc.35083. 

4.     Favale G, Donnarumma F, Capone V, Della Torre L, Beato A, Carannante D, Verrilli G, Nawaz A, Grimaldi F, De Simone MC, Del Gaudio N, Megchelenbrink WL, Caraglia M, Benedetti R, Altucci L, Carafa V. Deregulation of New Cell Death Mechanisms in Leukemia. Cancers (Basel). 2024 Apr 25;16(9):1657. doi: 10.3390/cancers16091657. 

5.     Wahab MA, Del Gaudio N, Gargiulo B, Quagliariello V, Maurea N, Nebbioso A, Altucci L, Conte M. Exploring the Role of CBX3 as a Potential Therapeutic Target in Lung Cancer. Cancers (Basel). 2024 Aug 30;16(17):3026. doi: 10.3390/cancers16173026. 

6.     Benedetti R, Altucci L. Phase separation rewires chromatin in breast cancer. Nat Cancer. 2024 Nov;5(11):1602-1604. doi: 10.1038/s43018-024-00843-9.

7.     Bove G, Crepaldi M, Amin S, et al. The m6A-independent role of epitranscriptomic factors in cancer. Int J Cancer. 2024; 155(10): 1705-1713. doi:10.1002/ijc.35067

2025

1.     Bove G, Babaei M, Bueno-Costa A, Amin S, Simonelli N, Benedetti R, Dell'Aversana C, Conte M, Montella L, Summa V, Brindisi M, Del Sorbo MR, Crepaldi M, Favale G, Profitos-Peleja N, Carafa V, Roué G, Ciardiello F, Capuano A, Stunnenberg HG, Megchelenbrink WL, Nebbioso A, Esteller M, Altucci L, Del Gaudio N. METTL16-mediated inhibition of MXD4 promotes leukemia through activation of the MYC-MAX axis. Oncogene. 2025 Nov;44(43):4159-4172. doi: 10.1038/s41388-025-03563-1.

2.     Papulino C, Crepaldi M, Favale G, Del Gaudio N, Benedetti R, Nebbioso A, Grieco M, Malavolta M, Sabbatinelli J, Capuano A, Martinelli E, Martini G, Nardone V, Cappabianca S, Ambrosino C, Paolisso G, Altucci L, Carafa V. "Aging and epigenetic implications in radiotherapy: The promise of BNCT". Ageing Res Rev. 2025 Aug;110:102786. doi: 10.1016/j.arr.2025.102786. 

3.     Massaro C, Sgueglia G, Muro A, Pieragostino D, Lanuti P, Cufaro MC, Giorgio C, D'Agostino E, Torre LD, Baglio SR, Pirozzi M, De Simone M, Altucci L, Dell'Aversana C. Vorinostat impairs the cancer-driving potential of leukemia-secreted extracellular vesicles. J Transl Med. 2025 Apr 10;23(1):421. doi: 10.1186/s12967-025-06361-1. 

4.     Noreen S, Simonelli N, Benedetti R, Carafa V, Grieco M, Ambrosino C, Dell'Aversana C, Nebbioso A, Conte M, Del Gaudio N, Altucci L. Unravelling the impact of the chromobox proteins in human cancers. Cell Death Dis. 2025 Apr 2;16(1):238. doi: 10.1038/s41419-025-07585-1.

5.     Sarno F, Conte M, Muro A, Dell'Aversana C, Sgueglia G, Carafa V, Del Gaudio N, Nebbioso A, Altucci L. Lysine demethylase (KDM) inhibitors for the treatment of cancer: a patent review (2015-present). Expert Opin Ther Pat. 2026 Jan;36(1):65-89. doi: 10.1080/13543776.2025.2600945. 

6.     Bove, G., Babaei, M., Bueno-Costa, A. et al. METTL16-mediated inhibition of MXD4 promotes leukemia through activation of the MYC-MAX axis. Oncogene 44, 4159–4172 (2025). https://doi.org/10.1038/s41388-025-03563-1

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