Early Detection: A Potential Cure for Cancer

Each year, nearly 1.5 million Americans are diagnosed with cancer, and more than one-third of these cases result in death. Indeed, cancer is responsible for one in every four deaths in the country.¹ Those affected by cancer know that it is highly treatable, but only if detected early; just ask the more than 11 million cancer survivors and their families.²

One of those survivors is North Carolina Rep. Bob Etheridge, who was diagnosed with melanoma. That experience led him to introduce a bill to promote early detection for cancer, which was passed by the U.S. House of Representatives in January. The bill designates May as Early Detection Month, and is designed to enhance public awareness of screening for all forms of cancer by encouraging activities to educate the public about early detection and cancer screening.¹ “I am thankful that my melanoma was caught and treated,” Etheridge says. “By passing legislation to designate public awareness of cancer screenings and early detection, we can make sure that all Americans have the chance I had to get treatment and survive. Early detection saves lives and focuses healthcare on prevention of diseases, rather than simply treating them after they have occurred.”

Etheridge isn’t alone in his quest. President Obama has pledged to conquer cancer “in our time,” and his first proposed budget included $6 billion for cancer research by the National Institutes of Health. This proposal will build on the ongoing progress that is being made in detecting cancer early enough to save lives. For example, statistics show that the risk of death from cancer in American men is 20 percent lower than it was 20 years ago. 2 Yet, while this is an improvement, the risk of death still remains too high. To answer this problem, an impressive amount of research is aimed at early detection, as well as the development of new diagnostic tools. Currently, two promising areas offer hope: molecular diagnostics that can be detected with genetic biomarkers and imaging diagnostics — both of which employ non-invasive and minimally intrusive techniques.

Molecular Diagnostics

Simply defined, molecular diagnostics is the use of DNA, RNA and proteins to identify biomarkers that can be used to distinguish abnormal from normal status. Biomarkers may include genetic, epigenetic, proteomic and metabolomic markers, as well as those derived from imaging and general physical examination-based techniques. The two leading research areas contributing to the identification of biomarkers are genomics and proteomics.³

Genomics is the study of complex sets of genes, how they are expressed in cells (what their level of activity is) and the role they play in biology. In cancer research, genomics is the study of a small network of genes and how they work together to influence a tumor’s biology and behavior. 4 For biomarker discovery using genomics, DNA samples for testing can be obtained least invasively from sputum samples, but alternatives include tissue biopsy, surgery samples and serum/plasma samples.³

Unfortunately, genomic-based biomarkers are limited compared with protein biomarkers. This is because the mRNA and protein levels don’t necessarily correspond, which means the genomic-based biomarker may not fully reflect the underlying characteristics of cancers. Protein biomarkers, on the other hand, can detect genetic alterations, such as chromosomal abnormalities, oncogenes and tumor-suppressor genes, which can play a role in early diagnosis and prediction of cancer progression.³

Identifying and analyzing protein patterns in the blood is a field of study called proteomics. The process involves extracting proteins in the blood, urine or other tissue to be analyzed by a technique known as mass spectrometry, which creates patterns of protein fragments.An artificial-intelligence computer program then sorts the unique protein signatures and identifies the discrepancies in protein patterns between people with and without cancer. Those proteins linked to cancer can then serve as biomarkers to detect early disease and predict responsiveness to therapy or the likelihood of recurrence. They also can be used to classify the genetic subtype of the cancerso that treatment can be better tailored to the individual.⁵

In the past 10 years, the rapid development of proteomic technologies has brought about a massive increase in the discovery of novel cancer biomarkers.⁶ According to the Fred Hutchinson Cancer Research Center (FHCRC), the key to a potentially cancer-free future lies in the blood, where proteins and other molecules hold critical information about cancer. The FHCRC was selected by the National Cancer Institute (NCI)to lead one of two research teams dedicated to developing simple blood tests to detect the earliest signs of cancer and other diseases, so they can be treated as early as possible, when cure rates are highest. The initial aim of the NCI-funded consortium is “to identify serum biomarkers — proteins in the blood that either alone or in combination are detected in altered amounts in people with cancer or who are at high risk of developing the disease.”⁵

While the study of proteomics still has a long way to go for the detection of many cancers, FHCRC scientists have already developed a blood test to predict whether leukemia will return after treatment, and they have identified a protein that could lead to a new blood test for ovarian cancer. Most recently, scientists identified two proteins in the blood that could become important prognostic markers for long-term survival in breast cancer patients.⁷

The FHCRC isn’t the only organization making headway in biomarker discovery using proteomics. The following are some interesting proteomics developments:

• Scientists have found that cancer patients produce antibodies that target abnormal glycoproteins(proteins with sugar molecules attached) made by their tumors. This suggests that antitumor antibodies in the blood may provide a fruitful source of sensitive biomarkers for cancer detection. The study, supported in part by the National Cancer Institute (NCI), part of the National Institutes of Health, appears in the Feb. 15, 2010, issue of the journal Cancer Research.⁸
• United Kingdom scientists have designed a method to detect prostate cancer using surface-enhanced resonance Raman scattering (SERRS). The researchers combined the technique with a biological method called an enzyme-linked immunosorbent assay (ELISA) to detect a prostate-specific antigen in which elevated levels in serum indicate the cancer’s presence. The process involved first analyzing antigen levels in human serum samples using ELISA, and then using gold nanoparticles with SERRS to measure antigen concentration. This resulted in detection of picograms per milliliter antigen levels, lower than the current limit of nanograms per milliliter in cancer screening. In the future, they hope to be able to use SERRS to detect multiple proteins that indicate the presence of disease.⁹
• Quanterix, a company created by Tufts University chemistry professor DavidWalt, is developing away to detect trace quantities of proteins in the blood that could be an early warning sign for cancer or a neurodegenerative disease like Alzheimer’s or Parkinson’s.The company’s newCEO,Dave Okrongly, says its test is about 1,000 times more sensitive than the gold-standard ELISA because proteins in the bloodstream generally come in trace amounts too small to be detected by the standard ELISA tests.The Quanterix system, on the other hand, is designed to detect thousands of single molecules simultaneously with proprietary chemistry and what the company calls “a relatively simple” instrument with a light source, optics, a digital camera and an automated handling system.

Outside the field of proteomics, some other interesting research is being conducted to identify biomarkers. A new technique known as dielectrophoresis (DEP) uses an electrical field to separate particles according to their differing electrical properties. American scientists are using this technique to separate live and dead leukemia cells to provide an automated system for early cancer detection. Yet, because conventional DEP requires direct contact between the electrodes and sample fluid, leading to problems such as contamination and bubble formation, these scientists have developed a new approach known as contactless-DEP in which the electrodes are separated from the sample by a thin barrier to avoid any problems. The scientists are now optimizing the device, which they say could allow selective separation of cells from biological fluids for cancer diagnosis and differentiation of cells at different stages of the disease.¹¹

Other studies conducted by ChromoCure and the Mayo Clinic have validated the theory of aneuploidy, a chromosomal theory of cancer. Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders (birth defects), and some cancer cells also have abnormal numbers of chromosomes. For some time, controversy has existed over whether aneuploidy is a cause or a consequence of cancer, and these studies point to the former. The study appeared in the Jan. 15, 2010, edition of Cancer Research.¹²

While these are just a tiny sampling of the number of molecular diagnostic studies currently in development, they show great promise. The ultimate goal of biomarkers, says Leland H. Hartwell, president and director at the FHCRC, is risk assessment that can lead to prevention and early detection leading to cures, and he uses an interesting metaphor when he likens disease prevention and early detection to“the continuous data acquisition occurring in commercial aircraft.” He explains: “With 40,000 flights a day in the U.S., it is very rare for a commercial plane to crash, and when it does, it is more often due to human error than mechanical failure. This is because 10,000 sensors are accumulating and reporting information, continuously providing early warning of a pending failure.” Hartwell asks, then, “Could we monitor our bodies with the same sophistication?” Science is showing that, in fact, it can. And, while it is a major piece of the puzzle for detecting and preventing cancer, it is not the whole picture.¹³

Imaging Diagnostics

Many have criticized the search for biomarkers for cancer because they believe biomarkers won’t be specific enough or they can lead to overdiagnosis or overtreatment. But, Hartwell says that those critics fail to appreciate other developments that can accompany better blood tests. “Finding cancer proteins in the blood will probably never be sufficient for a cancer diagnosis,” he says, “but it is sufficiently informative to warrant more expensive imaging tests that localize the abnormality.”¹³

Imaging technologies are currently available to screen for all kinds of potential illness, including cancer. The more publicized tools, of course, are full-body screening. These include electron beam tomography (EBT), CT scans employing a computer helical CAT scan (also known as spiral scanning), positron emission tomography (PET) scans and magnetic resonance imaging (MRI). The smallest cancers can now be detected through these scans, long before they might be visible on standard chest X-rays or other tests.

EBT. When undergoing EBT, patients lie fully clothed on a table while an electronic beam traverses the body area and produces three-dimensional images for examination by a technician or physician. These detailed graphics can be viewed from every possible angle, and images can be stored, filmed or transmitted. The major medical application for which this design technology was invented in the 1980s was for imaging the beating human heart, and other structures, such as arteries, that move several times their diameter during each heartbeat. An advantage of EBT scans is that they can be swept with far greater speed, which is important to prevent blurring of moving structures during the scan.¹⁴

Spiral CT. In spiral CT scans, the X-ray tube rotates around the reclining patient as the examination table moves forward through the scanner. The rotating tube, thus, provides a spiral view of the body. Spiral CT scanning can permit greater visualization of blood vessels and internal issues, such as those within the chest cavity.

Both EBT and spiral CT scans are rapid and non-intrusive for the patient, exposure to radiation is minimal, and results are provided within minutes.¹⁴

PET. A PET scan observes processes in the brain, heart and other internal organs, and its importance for early cancer detection is its ability to trace metabolic changes in cancer cells that are different from other tissues. In cancer cells, there are increased rates of blood flow, amino acid flow, DNA synthesis and glucose transport compared to normal tissues, and a PET scan can detect these changes within a high range of efficiency. 15 In recent years, some facilities have combined PET scans with CT scans into one procedure, which provides a more complete picture of a tumor’s location and growth or spread than either test alone. Researchers hope that PET/CT scanning will improve healthcare professionals’ ability to diagnose cancer, determine how far it has spread and follow patients’ responses to treatment.¹⁶

MRI. An MRI uses two safe and natural forces, a magnetic field and radio waves, to produce vivid images of internal body parts, including soft tissues, muscles, nerves and bones.¹⁷ Much like CT scans, an MRI can produce three-dimensional images of sections of the body, but an MRI is sometimes more sensitive than CT scans for distinguishing soft tissues.¹⁸ MRIs are commonly used to screen for breast cancer. In women with a high inherited risk of breast cancer, screening trials of MRI breast scans have shown that MRI is more sensitive than mammography for finding breast tumors.¹⁹

Other minimally invasive imaging technologies also are emerging. One of these is the WavSTAT Optical Biopsy System developed by SpectraScience, which is indicated for use as an adjunct to lower gastrointestinal (GI) endoscopy. The WavSTAT uses a spectrophotometry technique known as laser induced fluorescence (LIF) that shines a color laser light onto and excites tissues to emit a returning fluorescent signal, which indicates whether tissue is normal, precancerous or cancerous. Those tissues are then immediately analyzed by a software algorithm, allowing physicians to determine whether a biopsy should be taken.²⁰ This type of minimally invasive procedure goes one step further than non-invasive imaging technologies because, since the scope is already in place, a biopsy can immediately be taken.

The Future of Early Detection

“It is estimated that the pharmaceutical industry spends about $20 billion a year developing cancer therapeutics, most of which have marginal benefit,” says Hartwell. What’s surprising, though, is that “the investment in diagnostic approaches is minuscule in comparison with their potential impact on improving patient outcomes” — due not just to few technology advances or too little time. Instead, says Hartwell, there are other reasons, equally formidable. The Institute of Medicine has published a monograph on cancer biomarkers that identifies several challenges beyond the stage of discovering biomarkers. “First, reimbursement for new diagnostics is poor, a situation that discourages the commercial investment that is needed.[And,] current models for obtaining FDA approval for new diagnostics are nearly as difficult and costly as for the approval of drugs.”¹³

Despite these challenges, many scientists are forging ahead to discover further molecular diagnostics, as well as develop new imaging tools. Their efforts promise to bring about even greater success for early detection of all cancers, and could lead to the eventual eradication of cancer itself.