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The importance of cellular irrigation

If the cancer cells are poorly irrigated, they become quiescent (this is observed in the centre of the tumour). They also will receive less anticancer drugs and will be less sensitive to them.

This is one of the reasons why an initial surgical procedure to reduce the tumour volume is so important (as in ovarian carcinoma).

On the other hand, radiotherapy strongly modifies the vascularisation of and around the tumour. If relapse occurs inside the irradiated volume, the relapsing tumour is generally chemoresistant, due to deficient vascularisation (and perhaps also because of similar cross-resistance mechanisms between chemotherapy and radiotherapy).

Access to tumour cells is of utmost importance in order to eradicate them via chemotherapy.

A blood-brain barrier has been described which often renders cerebral tumours and metastases very resistant to chemotherapy due to the absence of penetration of the drug inside the tumour. Most anticancer drugs are large and very complex molecules with low solubility. Only small liposoluble molecules can cross this blood-brain barrier (however they may be difficult to transport by plasma).

There are breakages in this blood-brain barrier inside the tumour, however generally speaking, brain tumours are poorly irrigated, with central necrosis, and are therefore not penetrated by anticancer drugs brought by the blood stream.

Diagram representation of the blood-brain barrier. The endothelial cells of the capillaries (CE) are joined together by tight junctions (TJ) which can only be crossed by small molecules coming from the vascular lumen. The astrocyte feet are also joined by Gap junctions (GJ) which can be only crossed by lipophilic molecules towards the extracellular space where a neuron has been drawn.

Conversely, the use of intraperitoneal chemotherapy should allow an increased concentration of the drug close to the peritoneal metastases among ovarian or digestive tumours. However, this contact chemotherapy cannot penetrate a depth of more than a few millimetres, thus limiting the procedure.