Intratumor heterogeneity and its impact on drug distribution and sensitivity.
We provide an overview of the available information on the distribution of chemotherapeutics in human tumors, highlighting the progress made to assess the heterogeneity of drug concentrations in relation to the complex neoplastic tissue using novel analytical methods, e.g., mass spectrometry imaging. The increase in interstitial fluid pressure due to abnormal vascularization and stiffness of tumor stroma explains the variable and heterogeneous drug concentrations. Therapeutic strategies to enhance tumor drug distribution, thus possibly increasing efficacy, are discussed.
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Cancer Pharmacology, Department of Oncology, Milan, Italy.
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Fuso Nerini
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Cancer Pharmacology, Department of Oncology, Milan, Italy.
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L
Morosi
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Cancer Pharmacology, Department of Oncology, Milan, Italy.
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Zucchetti
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Cancer Pharmacology, Department of Oncology, Milan, Italy.
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Ballerini
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Biology and Treatment of Metastases, Department of Oncology, Milan, Italy.
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Giavazzi
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Laboratory of Cancer Pharmacology, Department of Oncology, Milan, Italy.
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D'Incalci
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D003952:Diagnostic Imaging / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents