Discovery of innovative predictive and prognostic biomarkers in cancer

Precision oncology requires access to patient-specific cancer information, which can be obtained both through traditional tissue biopsy and more recently by so-called “liquid biopsy” approaches, meaning analysis of tumor-derived biomarkers in body fluids, more commonly plasma samples. Our group has been exploring the potential of liquid biopsy in translational research for a number of cancer types, including among others lung, breast, urothelial and colorectal cancer. Among common solid tumors, NSCLC is probably the best example of successful clinical application of targeted therapies. Accordingly, genetic screening for actionable mutations or alterations in genes such as EGFR, ALK, ROS1 in plasma samples is current practice, as detection of such mutations enables prescription of certain targeted drugs, belonging to the family of tyrosine kinase inhibitors (TKI).
Biomarkers that can be assessed in plasma samples from cancer patients include both RNA markers and DNA markers, endowed with either prognostic or predictive value.


Research achievements

We have also started to use NGS and ddPCR technologies for quantitative measurements of the mutationalload in plasma and monitor its dynamic variations during therapy. These studies investigated whether molecular variations detected in cfDNA can precede radiologic or clinical responses. In parallel, we are evaluating circulating miRNA profiles and tumor-specific mRNA throughout treatment, with the goal of identifying correlations with response rates and the duration of clinical benefit. In this conceptual framework, we are also keen to investigate possible early biomarkers of resistance or adverse effects of immunotherapy.


Aims

In the future these “liquid biopsy” studies will evolve by including assessment of novel cancer-derived biomarkers as well as by performing interventional studies, underscoring the fact that clinical decision about treatment will be made based on assessment of some of these circulating biomarkers also in rare tumors, such as those occurring in NF1 patients. These studies will be integrated (when feasible) by tissue biomarkers analysis, aiming to interrogate by digital pathology, spatial omics and other upcoming cutting-edge techniques the still poorly understood heterogeneity of cancer.


5 Publications

  • Cavallari I, Grassi A, Del Bianco P, Aceti A, Zaborra C, Sharova E, Bertazzolo I, D'Agostino DM, Iafrate M, Ciminale V. Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-based Approach. Cancers (Basel). 2020 Oct 26;12(11):3133. doi: 10.3390/cancers12113133. PMID: 33114775
  • Rampazzo E, Cecchin E, Del Bianco P, Menin C, Spolverato G, Giunco S, Lonardi S, Malacrida S, De Paoli A, Toffoli G, Pucciarelli S, De Rossi A. Genetic Variants of the TERT Gene, Telomere Length, and Circulating TERT as Prognostic Markers in Rectal Cancer Patients. Cancers (Basel). 2020 Oct 25;12(11):3115. doi: 10.3390/cancers12113115.PMID: 33113831
  • Zulato E, Del Bianco P, Nardo G, Attili I, Pavan A, Boscolo Bragadin A, Marra L, Pasello G, Fassan M, Calabrese F, Guarneri V, Conte PF, Indraccolo S, Bonanno L. Longitudinal liquid biopsy anticipates hyperprogression and early death in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. Br J Cancer. 2022 Sep 29. doi: 10.1038/s41416-022-01978-1.PMID: 36175621
  • Boscolo Bragadin A, Del Bianco P, Zulato E, Attili I, Pavan A, Carlet J, Marra L, Guarneri V, Indraccolo S, Bonanno L. Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer. NPJ Precis Oncol. 2024 Oct 17;8(1):234. doi: 10.1038/s41698-024-00704-9. PMID: 39420036 
  • Pasello G, Pigato G, Scattolin D, Lando S, Potente S, Romualdi C, Roma A, Resi MV, Frega S, Ferro A, Dal Maso A, Bonanno L, Guarneri V, Lazzarini L, Indraccolo S. Baseline levels and dynamic changes of cfDNA, tumor fraction and mutations to anticipate the clinical course of small cell lung cancer (SCLC) patients treated with first-line atezolizumab and chemotherapy: an hypothesis generating study (CATS/ML43257). J Exp Clin Cancer Res. 2025. Jun 19;44(1):178. doi: 10.1186/s13046-025-03434-3. PMID: 40537796 


Funding 

SID 2023
5X1000 IOV


People involved (PI)

Vincenzo Ciminale, Full Professor
Stefano Indraccolo, Associate Professor
Silvia Giunco, Assistant Professsor
Federica Chiara, Assistant Professor


Group Members

Loredana Urso, staff Researcher, IOV
Evgenyia Sharova, staff Researcher, IOV
Marzia Morello, staff Researcher, IOV
Giulia Pigato, research fellow, University of Padova
Alessia Padovan, research fellow, University of Padova
Andrea Boscolo Bragadin, staff researcher, IOV
Elisabetta Lazzarini, staff researcher, IOV


Collaborators

Bonanno Laura
Dieci Maria Vittoria
Guarneri Valentina
Iafrate  Massimo
Pasello Giulia
Russo Francesco Paolo
Spolverato Gaia