High levels of two growth factors that protect tumours from the effects of chemotherapy may be a cause of drug resistance, say US researchers (Proceedings of the National Academy of Science 2000;97:8658).
This finding could lead to the development of drugs that counteract the effect of the growth factors, which would improve the effectiveness of chemotherapy and allow the use of lower doses of anticancer drugs, they say.
Dr Jessie Au (Ohio State university, Columbus, Ohio, US) and colleagues found that when both basic and acidic fibroblast growth factor were present at high levels in tumours, the two in combination seemed to induce resistance to anticancer agents.
Animal studies done by the researchers showed that the growth factors induced resistance to three anticancer drugs that had different chemical structures and mechanisms of action (paclitaxel, doxorubicin and 5-fluorouracil).
Suramin, an inhibitor of fibroblast growth factors, was then tested to see if it could increase the effectiveness of chemotherapy in mice with human lung tumours. The researchers found that chemotherapy alone reduced the size of the tumours but a combination of chemotherapy and suramin completely eliminated the lung tumours in five out of 12 mice and shrank tumours by an additional 10-fold in the remaining animals.
Commenting on the research, Dr Au said: "We are hopeful that inhibitors of fibroblast growth factors can make a patient's tumour more sensitive to traditional chemotherapeutic drugs, and plan to test this new therapeutic approach in patients."
Clinical trials using suramin to block growth factors are expected to begin later this summer. The trials will involve patients with non-small-cell lung cancer.