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A current concern for physicians looking to improve cancer treatment is the need for better methods for monitoring the development of malignant tissues and tumors. This would help physicians be able to personalize treatment for patients on an individual level. As Dr. Heitzer of the Institute of Human Genetics in Graz, Austria states, “methods are needed for a rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of [cancer] disease.”1
Traditionally, physicians diagnose solid tumors with an x-ray followed by a needle biopsy—a surgical procedure that inserts a needle into the potential tumorous mass to retrieve a small chunk of tissue. A pathologist processes and evaluates the tissue chunk for the presence of any tumor cells. A needle biopsy provides a snapshot of the tumor, but is not done routinely for cancers because it’s an invasive surgery.
Many groups are searching for a blood test that helps monitor the growth or shrinkage of a solid tumor. Since a patient’s health status is monitored via blood samples during chemotherapy treatments, researchers believe a blood test approach may be a viable option.1-3
Efficient monitoring for lymphomas and leukemias in blood
As expected, cancers of the white blood cells, like lymphomas and leukemia, are relatively easy to monitor with blood samples because many tumor cells are located in the blood. Physicians harvest a sample of blood and request a laboratory to sort the blood cells into its different cell types: red blood cells, T cells, B cells, macrophages, stem cells, neutrophils, etc. Some of the cells will be cancerous.
The laboratory separates the cancer cells from the normal blood cells and then characterizes the mutations. Identification of the cancer’s mutations help indicate which cancer treatment may provide the most benefit to an individual patient.
Based off this procedure, many groups are developing and evaluating methods to find tumor cells or tumor cell DNA in blood samples from patients with lung cancer, colon cancer, or other solid tumors.1-4 These samples are called liquid biopsies. However, finding cancer cells, like lung cancer cells, in blood is like searching for a needle in a haystack.
Dr. Marchetti from the Center of Predictive Medicine in Italy sums up the challenge: “As few as 1 circulating tumor cell may be found in the background of billions of peripheral white blood cells”.3
However, their group uses a system that harvests cancer cells from a sea of normal cells, which is more like using a magnet to find an iron needle in a haystack.
Advantages of liquid biopsies
Personalized Treatment.Scientists can then test these tumor cells, called circulating tumor cells, for mutations in critical genes, and personalize the treatment to the patient. Monitor Treatment Success.These liquid biopsies can show the response of the individual’s tumor to treatment: if the treatment is working, then the number of tumor cells will decline in the blood.2 If some of the cells develop resistance to the given treatment, this method can detect it soon.2 The oncologist can then determine the next most likely effective treatment and switch it.
Circulating lung cancer cells in blood
Marchetti’s recent article describes researchers’ ability to detect a specific mutation in cancer cells from 37 lung cancer patients.3
They checked the method on two types of control samples: blood samples from 12 healthy subjects and tumor cells from 10 breast cancer patients without the mutation.3
In a study that compared methods to monitor patients in a clinical trial, researchers isolated the circulating cancer cells using what’s called the Veridex CellSearch System. They worked to identify any mutations in specific genes of the lung cancer cells. They correctly detected mutations in 31 of the 37 patients (84%). Whether lung cancer cells with the mutation shed more cancer cells is unknown. The control samples showed no mutations, as expected.3
Several laboratories are working to improve the isolation of circulating cancer cells and detection of mutations in liquid biopsies. Weekly monitoring of the tumor’s response to therapy would help physicians to personalize cancer treatment to each individual. Hopefully it will become standard practice in the near future.
Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem 2015;61(1):112-123.
Cai LL, Ye HM, Zheng LM, Ruan RS, Tzeng CM. Circulating tumor cells (CTCs) as a liquid biopsy material and drug target. Curr Drug Targets 2014;15(10):965-972.
Marchetti A, Del Grammastro M, Felicioni L et al. Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment. PLoS One 2014;9(8):e103883.
Yoshioka Y, Kosaka N, Konishi Y et al. Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nat Commun 2014;53591.