Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology
Tumor diseases are characterized by high interindividual and intratumoral heterogeneity (ITH). The development and progression of neoplasms outline complex networks of extracellular and cellular signals that have yet to be fully elucidated. This narrative review provides a comprehensive overview of...
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2025-06-01
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| author | Stelvio Tonello Roberta Rolla Paolo Amedeo Tillio Pier Paolo Sainaghi Donato Colangelo |
| author_facet | Stelvio Tonello Roberta Rolla Paolo Amedeo Tillio Pier Paolo Sainaghi Donato Colangelo |
| author_sort | Stelvio Tonello |
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| description | Tumor diseases are characterized by high interindividual and intratumoral heterogeneity (ITH). The development and progression of neoplasms outline complex networks of extracellular and cellular signals that have yet to be fully elucidated. This narrative review provides a comprehensive overview of the literature related to the cellular and molecular mechanisms underlying the heterogeneity of the tumor mass. Furthermore, it examines the possible role of the tumor microenvironment in the development and support of the neoplasm, in order to highlight its potential in the construction of a diagnostic–therapeutic approach to precision medicine. Many authors underline the importance of the tumor microenvironment (TME) as it actively takes part in the growth of the neoplastic mass and in the formation of metastases and in the acquisition of resistance to anticancer drugs. In specific body districts, the ideal conditions occur for the TME establishment, particularly the inflammatory state, the recruitment of cell types, the release of specific cytokines and growth factors, hypoxic conditions. These components actively intervene by enabling tumor progression and construction of physical barriers shaped by the extracellular matrix that contribute to forming peripheral tolerance by intervention of myeloid precursors and the polarization of M2 macrophages. In recent years, ITH and the TME have assumed an important position in cancer research and pharmacology as they enable understanding the dense network of communication existing between the neoplasm and the surrounding environment, and to monitor and deepen the effects of drugs with a view to develop increasingly precise and effective therapies. In the last decade, knowledge of TME has been exploited to produce targeted molecular agents (inhibitory small molecules, monoclonal antibodies, gene therapy). Nonetheless, the bibliography shows the need to study ITH through new prognostic and predictive biomarkers (e.g., ctDNA and CTCs) and to increase its basic biology knowledge. Precision medicine is a new opportunity in the treatment of oncological diseases that is transforming the development of new drug approaches and their clinical use. Biology and biotechnologies are providing the bases for this revolution. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-bad50ef9182a46e1a88d2b7aa66eba002025-08-20T03:29:45ZengMDPI AGPharmaceuticals1424-82472025-06-0118691510.3390/ph18060915Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision OncologyStelvio Tonello0Roberta Rolla1Paolo Amedeo Tillio2Pier Paolo Sainaghi3Donato Colangelo4Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, ItalyClinical Chemistry Laboratory, Maggiore della Carità Hospital, 28100 Novara, ItalyClinical Chemistry Laboratory, Maggiore della Carità Hospital, 28100 Novara, ItalyDipartimento di Medicina Traslazionale, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, ItalyDipartimento di Scienze della Salute, Farmacologia, Scuola di Medicina, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, ItalyTumor diseases are characterized by high interindividual and intratumoral heterogeneity (ITH). The development and progression of neoplasms outline complex networks of extracellular and cellular signals that have yet to be fully elucidated. This narrative review provides a comprehensive overview of the literature related to the cellular and molecular mechanisms underlying the heterogeneity of the tumor mass. Furthermore, it examines the possible role of the tumor microenvironment in the development and support of the neoplasm, in order to highlight its potential in the construction of a diagnostic–therapeutic approach to precision medicine. Many authors underline the importance of the tumor microenvironment (TME) as it actively takes part in the growth of the neoplastic mass and in the formation of metastases and in the acquisition of resistance to anticancer drugs. In specific body districts, the ideal conditions occur for the TME establishment, particularly the inflammatory state, the recruitment of cell types, the release of specific cytokines and growth factors, hypoxic conditions. These components actively intervene by enabling tumor progression and construction of physical barriers shaped by the extracellular matrix that contribute to forming peripheral tolerance by intervention of myeloid precursors and the polarization of M2 macrophages. In recent years, ITH and the TME have assumed an important position in cancer research and pharmacology as they enable understanding the dense network of communication existing between the neoplasm and the surrounding environment, and to monitor and deepen the effects of drugs with a view to develop increasingly precise and effective therapies. In the last decade, knowledge of TME has been exploited to produce targeted molecular agents (inhibitory small molecules, monoclonal antibodies, gene therapy). Nonetheless, the bibliography shows the need to study ITH through new prognostic and predictive biomarkers (e.g., ctDNA and CTCs) and to increase its basic biology knowledge. Precision medicine is a new opportunity in the treatment of oncological diseases that is transforming the development of new drug approaches and their clinical use. Biology and biotechnologies are providing the bases for this revolution.https://www.mdpi.com/1424-8247/18/6/915precision medicineintratumor heterogeneitytumor microenvironmentmolecular targetedpharmacological therapy |
| spellingShingle | Stelvio Tonello Roberta Rolla Paolo Amedeo Tillio Pier Paolo Sainaghi Donato Colangelo Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology Pharmaceuticals precision medicine intratumor heterogeneity tumor microenvironment molecular targeted pharmacological therapy |
| title | Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology |
| title_full | Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology |
| title_fullStr | Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology |
| title_full_unstemmed | Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology |
| title_short | Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology |
| title_sort | microenvironment and tumor heterogeneity as pharmacological targets in precision oncology |
| topic | precision medicine intratumor heterogeneity tumor microenvironment molecular targeted pharmacological therapy |
| url | https://www.mdpi.com/1424-8247/18/6/915 |
| work_keys_str_mv | AT stelviotonello microenvironmentandtumorheterogeneityaspharmacologicaltargetsinprecisiononcology AT robertarolla microenvironmentandtumorheterogeneityaspharmacologicaltargetsinprecisiononcology AT paoloamedeotillio microenvironmentandtumorheterogeneityaspharmacologicaltargetsinprecisiononcology AT pierpaolosainaghi microenvironmentandtumorheterogeneityaspharmacologicaltargetsinprecisiononcology AT donatocolangelo microenvironmentandtumorheterogeneityaspharmacologicaltargetsinprecisiononcology |