The role of CXCL12 axis in pancreatic cancer: New biomarkers and potential targets

Michela Roberto; Giulia Arrivi; Mattia Alberto Di Civita; Giacomo Barchiesi; Emanuela Pilozzi; Paolo Marchetti; Daniele Santini; Federica Mazzuca; Silverio Tomao

doi:10.3389/fonc.2023.1154581

The role of CXCL12 axis in pancreatic cancer: New biomarkers and potential targets

Front Oncol. 2023 Mar 23:13:1154581. doi: 10.3389/fonc.2023.1154581. eCollection 2023.

Authors

Michela Roberto¹, Giulia Arrivi², Mattia Alberto Di Civita¹, Giacomo Barchiesi¹, Emanuela Pilozzi³, Paolo Marchetti⁴, Daniele Santini¹, Federica Mazzuca², Silverio Tomao¹

Affiliations

¹ Oncology Unit (UOC) Oncologia A, Department of Radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
² Oncology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
³ Department of Clinical and Molecular Medicine, Anatomia Patologica Unit, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
⁴ Scientific Direction, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy.

Abstract

Introduction: Chemokines are small, secreted peptides involved in the mediation of the immune cell recruitment. Chemokines have been implicated in several diseases including autoimmune diseases, viral infections and also played a critical role in the genesis and development of several malignant tumors. CXCL12 is a homeostatic CXC chemokine involved in the process of proliferation, and tumor spread. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, that is still lacking effective therapies and with a dramatically poor prognosis.

Method: We conducted a scientific literature search on Pubmed and Google Scholar including retrospective, prospective studies and reviews focused on the current research elucidating the emerging role of CXCL12 and its receptors CXCR4 - CXCR7 in the pathogenesis of pancreatic cancer.

Results: Considering the mechanism of immunomodulation of the CXCL12-CXCR4-CXCR7 axis, as well as the potential interaction with the microenvironment in the PDAC, several combined therapeutic approaches have been studied and developed, to overcome the "cold" immunological setting of PDAC, like combining CXCL12 axis inhibitors with anti PD-1/PDL1 drugs.

Conclusion: Understanding the role of this chemokine's axis in disease initiation and progression may provide the basis for developing new potential biomarkers as well as therapeutic targets for related pancreatic cancers.

Keywords: CXCL12; CXCR4; CXCR7; biomarkers; chemokines; pancreatic ductal adenocarcinoma (PDAC); tumor micreoenvironment (TME).

Publication types

Review