Drug penetration in solid tumours

  title={Drug penetration in solid tumours},
  author={Andrew I. Minchinton and Ian F. Tannock},
  journal={Nature Reviews Cancer},
To be most effective anticancer drugs must penetrate tissue efficiently, reaching all the cancer cells that comprise the target population in a concentration sufficient to exert a therapeutic effect. Most research into the resistance of cancers to chemotherapy has concentrated on molecular mechanisms of resistance, whereas the role of limited drug distribution within tumours has been neglected. We summarize the evidence that indicates that the distribution of many anticancer drugs in tumour… 

Strategies to improve drug distribution in solid tumor

The potential strategies to improve the drug distribution by modifying factors such as tumor vessels, tumor blood flow, tumor stroma, tumor cells, interstitial fluid pressure (IFP), and drug properties are discussed.

Targeted Drug Delivery and Penetration Into Solid Tumors

Promising approaches to achieve this goal are based on the use of Asn‐Gly‐Arg‐containing peptides as ligands for drug delivery and of NGR‐TNF, a peptide‐tumor necrosis factor‐α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma.

Principles in the design of ligand-targeted cancer therapeutics and imaging agents

This Review describes the major principles in the design of ligand-targeted drugs and provides an overview of lig and–drug conjugates and ligand–imaging-agent conjugate that are currently in development.

Drug resistance and the solid tumor microenvironment.

How the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumormicroenvironment are described.

Barriers to drug delivery in interventional oncology.

Tumour cells resistance in cancer therapy

The molecular mechanisms involved in chemoresistance are described, discussing the mechanisms of resistance related to tumour microenvironment, as well as their intracellular mechanisms.

Limited Tissue Penetration of Taxanes: A Mechanism for Resistance in Solid Tumors

Results indicate that limited distribution is an important mechanism of tumor resistance to taxanes.

Polymeric drug delivery systems for localized cancer chemotherapy

This review focuses on both natural and synthetic biodegradable polymers that have been explored for localized chemotherapy, exploring their advantages, disadvantages, and clinical potential while citing examples of their use in pre-clinical development.

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

This work suggests a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.



Penetration of anticancer drugs through solid tissue: a factor that limits the effectiveness of chemotherapy for solid tumors.

Multicellular layers were grown in vitro on Teflon membranes from EMT6 murine and MCF7 human tumors and have been used to quantitate the penetration of four widely used anticancer drugs through solid tissue.

Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy.

The results suggest limited ability of anticancer drugs to reach tumor cells that are distant from blood vessels and may be an important cause of clinical resistance of solid tumors to chemotherapy.

Aspects of cytotoxic drug penetration, with particular reference to anthracyclines

  • D. KerrS. Kaye
  • Biology, Medicine
    Cancer Chemotherapy and Pharmacology
  • 2004
Experimental data indicate that drug penetration barriers may be an important determinant of cytotoxic drug efficacay, even in spheroids of only a few hundred microns in diameter, which would equate with those micrometastases which are the target of adjuvant chemotherapy in a wide range of tumour types.

Diversity of penetration of anti‐cancer agents into solid tumours

Current state of knowledge did not allow reliable prediction of the classification based on chemical structure or mechanism of action of anti‐cancer agents in well‐ and poorly‐perfused tumour regions.

The penetration of anticancer drugs through tumor tissue as a function of cellular adhesion and packing density of tumor cells.

Impaired penetration of anticancer agents through MCLs derived from the tightly packed cell lines and relative resistance to killing of cells within them by doxorubicin treatment strengthen the role of tumor cell adhesion and packing density as contributing to drug resistance.

Tumour stem cells and drug resistance

Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might lead to new therapeutic targets and better anticancer strategies.

Factors that influence the penetration of methotrexate through solid tissue

Examination of studies of the penetration of radiolabelled methotrexate through multicellular layers of murine EMT‐6 and human MCF‐7 cells grown on semiporous teflon membranes provides evidence that tissue penetration of metotrexate is through the extracellular space, that its distribution in solid tissue may be limited and that it may be possible to improve its tissue penetration.

Direct Assessment of Drug Penetration into Tissue Using a Novel Application of Three-Dimensional Cell Culture

A novel multilayered cell culture-based assay, which detects the penetration of anticancer drugs based on their effect within tissue, and could be applied as a simple anticancer drug development screen to discover drugs that exhibit desirable penetration properties.

Evaluation of a novel in vitro assay for assessing drug penetration into avascular regions of tumours.

Modifications made to a recently published assay are described that broadens the scope for assessing drug penetration during the early stages of drug development and to characterize the ability of various drugs to penetrate multicell layers, suggesting that the extent of drug metabolism is one factor that determines the rate at which drugs penetrate multICEll layers.

The Distribution of the Anticancer Drug Doxorubicin in Relation to Blood Vessels in Solid Tumors

Limited distribution of doxorubicin in solid tumors is an important and neglected cause of clinical resistance that is amenable to modification and can be adapted to studying the distribution of other drugs within solid tumors and the effect of strategies to modify their distribution.