How Cancer Drugs Make Cancer Worse

You’d think that a tumour shrinking would be considered good news for anyone suffering from cancer. Maybe not. Scientists have found that a type of cancer treatment aimed at shrinking tumours can actually make them spread more efficiently and kill patients quicker.

Choking off a tumour’s blood supply with an approach called anti-angiogenesis is the mechanism of many cancer drugs, but a new study says it might have the frightening side effect of causing tumours to metastasize aggressively.

Anti-antiogenesis is the fundamental function behind many widely used cancer drugs. For the study, the researchers looked at imatanib (brand name Gleevec), a leukaemia drug and sunitinib, (brand name Sutent), a treatment for gastrointestinal tumours.

I spoke to Dr Raghu Kalluri, one of the study’s authors and chief of the matrix biology division at Beth Israel Deaconess Medical Center in Boston. He said when focusing on tumour growth, the treatment results looked good. Tumours shrunk. But if you looked at the big picture, making tumours smaller didn’t mean the cancer was being controlled. It was actually spreading.

“Whatever manipulations we’re doing to tumours can inadvertently do something to increase the tumour numbers to become more metastatic, which is what kills patients at the end of the day,” Kalluri said.

The paper was published in the January 17 issue of Cancer Cell and was performed in mice genetically engineered to have breast cancer. When they induced anti-angiogenesis, they saw a 30 per cent decrease in the volume of each tumour over 25 days. But the number of tumours that had metastasized to the lungs tripled compared to untreated control mice.

Kalluri and his team performed a previous study in humans that found breast cancer patients with fewer cells called pericytes, which support the walls of veins, were less likely to survive their cancer. It turns out those are the cells damaged by some anti-angiogenesis drugs. By studying the mice they found that those pericytes are important because without them tumours become weak and leaky. And that causes cancer cells to launch survival mechanisms: the researchers found a fivefold increase in factors inside the pericyte-lacking cells that promote cell migration and growth.

In plainer terms, big tumours are less likely to spread, which is pretty disturbing. I’ve had several family members who died at the hands of cancer shortly after the “good news” that doctors had “shrunk the tumour!” Was that tumour shrinkage actually what killed them?

It’s possible, Kalluri says. But it’s important to note that the drugs used in the study, Gleevec and Sutent, are good at the job the FDA approved them for. It’s when doctors decide to use cancer drugs “off-label” (the FDA approves drugs for specific uses, but they can’t tell doctors how to use the drugs) indications that the treatment could be worse than the disease.

“If cancer drugs are used randomly against all kinds of cancer without thinking about all the biology of the tumour, it could lead to a poor prognosis,” Kalluri told me.

The study isn’t an indictment of all anti-angiogenic cancer drugs however. Avastin, the most popular cancer drug in the world, is also based on anti-angiogenesis but doesn’t target pericytes. Rather, it targets endothelial cells, which are on the outside of blood vessels, whereas pericytes line the inside. In November, the FDA revoked its approval for using Avastin to treat breast cancer against the pleas of patients and their families. But that decision was unrelated to Kalluri’s study — the FDA simply found that the drug wasn’t working all that well for breast cancer.

That said, Dr Kalluri wasn’t completely sure whether damaging endothelial cells might also cause metastasis. But it’s important, he said, for doctors to remember that tumours contains lots of types of cells, and they’re not all bad.

“Seventy to eighty per cent of cells in a breast tumours are non-cancer cells,” he said. “Are they all bad? Some of them there to protect us.”

[Cancer Cell]

Image: Shutterstock/BioMedical