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Slipping Past Cancer's Barriers

Mauro Ferrari

The State of the Fight

The current state of cancer treatment can tell us about how the disease operates, and why mass transport is such a key factor in cancer progression. Much clinical progress has been recorded for several cancer types, especially in those for which oncologists have developed broadly deployable screening techniques. Pap tests for cervical cancer, mammograms for breast cancer, and colonoscopies for intestinal cancer have substantially reduced the burden of death and suffering for these three manifestations of the disease. Unfortunately, there are no equivalent early screening techniques for cancers of the lung, ovary, brain, pancreas, and liver, to cite a few of the most deadly tumor types.

When cancer is detected early enough, it can often be completely cured by surgical removal or radiotherapy. If it is not destroyed in time, however, eventually most primary tumors will send their envoys to establish a metastatic colony in a distant organ—and usually by the time we detect the first metastasis there are many others in multiple body locations. At that point the cancer is generally incurable. With recent advances in chemotherapy and biological therapy (which stimulate the immune system to attack cancer), doctors can extend a patient’s life by weeks or months, and protect the quality of life as well, to a minor extent. But the sad reality is that the current cure rates for metastatic disease still sit where they have been throughout the history of humankind—in a neighborhood near zero.

The central reason for this agonizingly slow progress is that metastases are exceedingly difficult to treat. Surgery is ineffective against them, because of their sheer numbers. Cancer specialists often do not even know where all the metastases are in the body: Radiological imaging reveals some of them, but usually there are many more than can be detected. They may be just too small to be seen by our instruments at the time we run tests, but they will grow rapidly, sometimes in a matter of weeks.

Above all, metastases are diverse. One might think that a breast cancer metastasis to the lungs should be similar to the primary tumor, and respond to the same drugs. This result is sometimes the case, but many times it is not, and over a sufficiently long period of time there always are metastases that share little with their tumor of origin.

Cancer is genetically unstable by its very nature: The daughter cells of a cancer carry a large number of genetic mutations, so their entire progeny has a devastating spectrum of differences that include their vulnerability to drugs. Therefore, when we use a medication that was effective against the primary tumor, we may initially succeed in controlling the metastases, but over time the cells that have a reduced response to the treatment will take over and cause the near totality of cancer deaths. That limitation is one of the reasons my colleagues and I started looking for a fundamentally different way to attack and defeat cancer.

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