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Cancer from eating salted fish tested early from blood test

Liquid Biopsy

Fast DNA-sequencing machines are leading to simple blood tests for cancer.

 

Everything about China is big, including its cancer problem. In some wealthier cities, like Beijing, cancer is now believed to be the most frequent killer. Air pollution, high rates of smoking, and notorious “cancer villages” scarred by industrial pollution are increasing death rates around the country. Liver cancer in particular is four times as prevalent as it is in the West, in part because one in 14 people in China carry hepatitis B, which puts them at risk. Of all the people worldwide who die of cancer each year, some 27 percent are Chinese.

Liquid Biopsy
  • BreakthroughA blood test to catch cancer early.
  • Why It MattersCancer kills some eight million people a year around the world.
  • Key PlayersDennis Lo, Chinese University of Hong Kong
    Illumina
    Bert Vogelstein, Johns Hopkins

In December, I traveled by metro from Shenzhen to Hong Kong. There I had arranged to meet Dennis Lo, a doctor who has worked for nearly 20 years on a technique called the “liquid biopsy,” which is meant to detect liver and other cancers very early—even before symptoms arise—by sequencing the DNA in a few drops of a person’s blood.

Lo appeared fastidiously dressed as usual in a sharp blazer, a habit that called to mind formal dinners at the University of Oxford, where he studied in the 1980s. He is well known for having been the first to show that a fetus sheds bits of its DNA into the bloodstream of its mother. That finding, first made in 1997, has in recent years led to a much safer, simpler screening test for Down syndrome. By now more than one million pregnant women have been tested.

Today Lo is competing with labs around the world to repeat that scientific and commercial success by developing cancer screening tests based on a simple blood draw. That’s possible because dying cancer cells also shed DNA into a person’s blood. Early on, the amount is vanishingly small—and obscured by the healthy DNA that also circulates. That makes it difficult to measure. But Lo says the objective is simple: an annual blood test that finds cancer while it’s curable.

Cancers detected at an advanced stage, when they are spreading, remain largely untreatable. In the United States, early detection is behind medicine’s most notable successes in applying technology to cut deaths from common cancers. Half of the steep decline in deaths from colorectal cancer is due to screening exams like colonoscopies.

Lo’s hospital is involved in two of the largest studies anywhere to prove that DNA analysis can also act as a screening test. The researchers are following a thousand people with hepatitis B to see if the DNA test can spot liver tumors before an ultrasound can. An even larger study is on nasopharyngeal carcinoma, a cancer that starts in the upper part of the throat. It’s rare elsewhere in the world, but in south China men have a one in 60 chance of contracting it in their ­lifetimes.

This cancer appears to be linked to eating salted fish, as well as to a genetic susceptibility among Chinese and to infection by the Epstein-Barr virus, the germ that causes mononucleosis. The role of the virus, says Lo, creates a special situation. The test he developed searches for easy-to-spot viral DNA that dying cancer cells release into a person’s plasma.

The study involves 20,000 healthy middle-aged men recruited in Hong Kong, and it’s halfway done. Among the first 10,000 men screened, the researchers picked up 17 cases of cancer—13 of those at stage I, the earliest kind. Nearly all these men have now beaten the cancer with radiation treatment. The typical survival rate is less than 70 percent if patients seek out a doctor only when they have the most advanced symptoms, like a mass in the neck. “They would normally be just walking on the street not knowing that there was a time bomb waiting to go off, and now we have alarmed them,” says Lo. As he sees it, every man in south China could be screened. One private hospital in Hong Kong has started offering the test already. “We believe it will save lives,” he says.

Lo’s lab is now locked in a technology race with scientists at other institutions, including Johns Hopkins University, to see if these ideas can turn into a general-purpose test for nearly any cancer, not only those involving a virus. The approach relies on gene-sequencing machines, which rapidly decode millions of short fragments of DNA that are loose in the bloodstream. The results are compared with the reference map of the human genome. Researchers can then spot the specific patterns of rearranged DNA that are telltale signs of a tumor.

Lo showed me several older sequencing machines during a tour of his laboratory, located at the Chinese University of Hong Kong. He says that the next generation of DNA sequencers, some no larger than a cell phone, could allow routine screening for cancer to become less expensive and far more widely used. For the time being, the cost of the DNA test being tried out on people at risk for liver cancer is still too high for routine use. Lo notes that the fetal tests were similarly expensive at first but that prices have since declined to as little as $800. That’s led to much wider use. “The same thing should happen [with cancer],” he says.

Building on the foundations put in place by doctors like Lo, commercial interest in liquid biopsies has recently started to explode. Eric Topol, a professor of genomics at the Scripps Research Institute, predicted this January that the technology, applied to cancer and other diseases, will become the “stethoscope for the next 200 years.” Jay Flatley, CEO of Illumina, the San Diego company that builds fast gene-­sequencing machines, told investors this year that the market for such tests could be worth at least $40 billion. Calling the technology “perhaps the most exciting breakthrough” in cancer diagnostics, he said his company would begin offering researchers a liquid-biopsy test kit to facilitate the search for signs of cancer.

In addition to screening for cancer, liquid biopsies could be a way to help people already fighting the disease. Doctors can pick a drug according to the specific DNA mutation driving a cancer forward. Tests to identify the mutation are sometimes done on tissue taken from a tumor, but a noninvasive blood test would be appropriate in more cases. Lo told me that 40 percent of Chinese lung cancer patients have a mutation in one gene, EGFR, that would make them eligible for new targeted drugs.

Cancer comes in many types, and Lo says that for each, researchers must methodically make their case that liquid biopsies can really save lives. He believes he’s close with nasopharyngeal cancer. “If you can screen and prognosticate in very common cancer types, that is the time when it will go mainstream,” he says.

—Michael Standaert

Published by connie dello buono

Connie Dello Buono is based in Sunnyvale California. Her first ebook is about women's health, Birthing Ways Healing Ways and her recent one is about cancer prevention, Curated Healing Ways. She had helped women have holistic childbirth as childbirth educator, founded Motherhealth, to serve seniors in the bay area with holistic caregivers and blogs at www.clubalthea.com with more than 10,000 health and finance related posts. Connie trains her own caregivers, which are the favorites of most bay area seniors who are home bound and alone. She is active in the rehab and nursing facilities, volunteering on music and movement for seniors. She is a member of Lion's club and offered scholarships to students in the Philippines. She is active at churchinsunnyvale.us and has Fridays Bible home study in Sunnyvale using the recovery version of the Bible , free at biblesforamerica.us She loves dancing and teaching and her courses can be found at https://teachclub.com/@thriveafter60 She is California Life Insurance licensed providing life insurance for older adults with health issues and helping women retire safely with income for life. at menloassetca.com , she helps with 401k rollover. 3 Benefit plans - Mortgage protection using term life insurance to pay for mortgage balance in event of death - Final Expense plan using Single Issue Whole Life Insurance, with cash back, disability benefit and guaranteed in the presence of health issues - Fixed Index Annuity retirement plan for safe, accessibility, less fees, less taxes, avoids probate as it goes directly to beneficiaries, rate of return with no downside market participation. She brings compassion and understanding to the needs of her clients, bringing holistic approach in health and life insurance. Her goal is to free families from worries especially during covid with caregivers and life insurance in the presence of health issues, especially for women. She can be reached at 408-854-1883 , motherhealth@gmail.com

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