Imagine a simple blood test that could flag most kinds of cancers at the earliest, most curable stage. Liquid biopsies could, in theory, detect a tumor (肿瘤) well before it could be found by touch, symptoms or imaging. Blood tests could avoid the need for surgeons to cut tissue samples and make it possible to reveal cancer hiding in places needles and scalpels cannot safely reach. They could also determine what type of cancer is taking root to help doctors decide what treatment might work best to destroy it.
Liquid biopsies are not yet in hand, because it is hard to find definitive cancer signals in a tube of blood, but progress in recent years has been impressive. Last year the journal Science published the first big prospective study of a liquid biopsy for DNA and proteins from multiple types of cancers. Though far from perfect, the blood test called CancerSEEK found 26 tumors that had not been discovered with conventional screenings.
Liquid biopsies can rely on a variety of biomarkers in addition to tumor DNA and proteins, such as free-floating cancer cells themselves. But what makes the search difficult, Ana Robles, a cancer biologist of the National Cancer Institute, explains, is that "if you have an early-stage cancer or certain types of cancer, there might not be a lot of tumor DNA," and tests might miss it. The ideal blood test will be both very specific and very sensitive so that even tiny tumors can be found. To tackle this challenge, CancerSEEK looks for cancer-specific mutations (突变) on 16 genes, and for eight proteins that are linked to cancer and for which there are highly sensitive tests.
Simple detection is not the only goal. An ideal liquid biopsy will also determine the likely location of the cancer so that it can be treated. "Mutations are often shared among different kinds of cancer, so if you find them in blood, you don't know if that mutation is coming from a stomach cancer or lung cancer," says Anirban Maitra, a cancer scientist at the Anderson Cancer Center. To solve that problem, some newer liquid biopsies look for changes in gene expression. Such changes, Maitra notes, are "more organ-specific".
On the nearer horizon are liquid biopsies to help people already diagnosed with cancer. Last year the government approved the first two such tests, which scan for tumor DNA so doctors can select mutation-targeted drugs. Scientists are working on blood tests to detect the first signs of cancer recurrence (复发) in patients who have completed treatment. This work is moving fast, but does it save lives?
That is the question companies such as Thrive and Grail must answer for their broadly ambitious screening tests. "These companies have to prove that they can detect early cancer and, more important, that the early detection can have an impact on cancer survival," Maitra observes.
