Project Publications

Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations.
Castro-Giner F, Gkountela S, Donato C, Alborelli I, Quagliata L, Ng CKY, Piscuoglio S, Aceto N

» Abstract


The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample or other body fluids, allowing the interrogation of tumor-derived material including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) fragments that are present at a given time point. In this short review, we discuss a few studies that summarize the state-of-the-art in the liquid biopsy field from a diagnostic perspective and speculate on current challenges and expectations of implementing liquid biopsy testing for cancer diagnosis and monitoring in the clinical setting.

Diagnostics (Basel). 2018 May 9;8(2):31. doi: 10.3390/diagnostics8020031LINK

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Bioprinting Vasculature: Materials, Cells and Emergent Techniques.
Tomasina C, Bodet T, Mota C, Moroni L, Camarero-Espinosa S.

» Abstract


Despite the great advances that the tissue engineering field has experienced over the last two decades, the amount of in vitro engineered tissues that have reached a stage of a clinical trial is limited. While many challenges are still to be overcome, the lack of vascularization represents a major milestone if tissues bigger than approximately 200 µm are to be transplanted. Cell survival and homeostasis are to a large extent conditioned by the oxygen and nutrient transport (as well as waste removal) by blood vessels on their proximity and spontaneous vascularization in vivo is a relatively slow process, leading all together to necrosis of implanted tissues. Thus, in vitro vascularization appears to be a requirement for the advancement of the field. One of the main approaches to this end is the formation of vascular templates that will develop in vitro together with the targeted engineered tissue. Bioprinting, a fast and reliable method for the deposition of cells and materials in a precise manner, appears like an excellent fabrication technique. In this review, we provide a comprehensive background to the fields of vascularization and bioprinting, providing details on the current strategies, cell sources, materials, and outcomes of these studies.

Materials (Basel). 2019 Aug 23;12(17):2701. doi: 10.3390/ma12172701. LINK

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Therapeutic vascularization in regenerative medicine.
Gianni-Barrera R, Di Maggio N, Melly L, Burger MG, Mujagic E, Gürke L, Schaefer DJ, Banfi A.

» Abstract

Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, the uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.

Stem Cells Transl Med. 2020 Apr;9(4):433-444. doi: 10.1002/sctm.19-0319. Epub 2020 Jan 10. LINK

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Circulating Tumor Cell-Neutrophil Tango along the Metastatic Process.
Saini M, Szczerba BM, Aceto N.

» Abstract

The crosstalk between cancer cells and the immune system is crucial for disease progression and its therapeutic targeting is providing exciting results, in particular with newly developed immune checkpoint inhibitors. Current approaches primarily focus on cellular interactions occurring between tumor cells and T lymphocytes; however, recent data highlight a crucial role of neutrophils in support of tumor progression and suggest yet unexplored treatment opportunities. In this review, we summarize the current understanding of those interactions that occur between neutrophils and cancer cells, focusing on both protumor and antitumor activities of neutrophils at different stages of cancer progression. These include infiltration of neutrophils into the primary tumor, their interactions with circulating tumor cells (CTC) within the bloodstream, and their involvement in the establishment of a metastatic niche. Additionally, we discuss how further investigation of CTCs and their interacting immune cell partners may point towards novel immune checkpoint inhibition strategies and provide new insights on the efficacy of already existing immunotherapies.

Cancer Res. 2019 Dec 15;79(24):6067-6073. doi: 10.1158/0008-5472.CAN-19-1972. Epub 2019 Sep 16. LINK

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To Be Taken in Count: Prostatic Tumor Cells Break Free upon Needle Biopsy.
Saini M, Aceto N.
Clin Chem. 2020 Jan 1;66(1):6-8. doi: 10.1373/clinchem.2019.311696. LINK

 

3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization.
Vitale C, Fedi A, Marrella A, Varani G, Fato M, Scaglione S.

» Abstract

Despite the great advances that the tissue engineering field has experienced over the last two decades, the amount of in vitro engineered tissues that have reached a stage of a clinical trial is limited. While many challenges are still to be overcome, the lack of vascularization represents a major milestone if tissues bigger than approximately 200 µm are to be transplanted. Cell survival and homeostasis are to a large extent conditioned by the oxygen and nutrient transport (as well as waste removal) by blood vessels on their proximity and spontaneous vascularization in vivo is a relatively slow process, leading all together to necrosis of implanted tissues. Thus, in vitro vascularization appears to be a requirement for the advancement of the field. One of the main approaches to this end is the formation of vascular templates that will develop in vitro together with the targeted engineered tissue. Bioprinting, a fast and reliable method for the deposition of cells and materials in a precise manner, appears like an excellent fabrication technique. In this review, we provide a comprehensive background to the fields of vascularization and bioprinting, providing details on the current strategies, cell sources, materials and outcomes of these studies.

Polymers (Basel). 2020 Oct 24;12(11):E2467. doi: 10.3390/polym12112467. LINK

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