New model establishes guidelines for earlier cancer detection
Tumors can grow for 10 years or longer before currently available blood tests will detect them, a new mathematical model developed by Stanford University School of Medicine scientists indicates. The analysis, which was restricted to ovarian tumors but is broadly applicable across all solid tumor types, will be published online Nov. 16 in Science Translational Medicine.
"The study's results can be viewed as both bad and good news," said Sanjiv "Sam" Gambhir, MD, PhD, professor and chair of radiology and the study's senior author. (Sharon Hori, PhD, a postdoctoral scholar in Gambhir's laboratory, is the lead author.)
The bad news, Gambhir said, is that by the time a tumor reaches a detectable size using today's available blood tests, it is likely to have metastasized to other areas of the body, making it much more deadly than if it had been caught early on. "The good news is that we have, potentially, 10 or even 20 years to find the tumor before it reaches this size, if only we can improve our blood-based methods of detecting tumors," he said. "We think our mathematical model will help guide attempts to do that."
The study advances previous research about the limits of current detection methods. For instance, it is strikingly consistent with a finding reported two years ago by Stanford biochemistry professor Patrick Brown, MD, PhD, that current ovarian cancer tests could not detect tumors early enough to make a significant dent in the mortality rate. There is a push to develop more-sensitive diagnostic tests and find better biomarkers, and Gambhir's new model could be an essential tool in this effort. It for the first time connects the size of a tumor with blood biomarker levels being shed by that tumor.
To create their model, Gambhir and Hori used mathematical models originally developed to predict the concentration of drugs injected into the blood as they move in and out of the bloodstream. The investigators linked these to additional models of tumor cell growth.
Tumors don't secrete drugs, but they can shed telltale molecules into surrounding tissue, from which those substances, known as biomarkers, diffuse into the blood. Some biomarkers may be made predominantly by tumor cells, while others exclusively by them. Either way, these substances can be measured in the blood as proxies for a tumor.
Some biomarkers are in wide use today. One is the well-known PSA, for prostate cancer. Another is CA125, for ovarian cancer. But these and other currently used blood tests for cancer biomarkers weren't specifically developed for early detection, and are generally more effective for relatively noninvasive monitoring of the progress of late-stage tumors or their response to treatment. (Rising blood levels of the substance indicate that the tumor is growing, while declining levels denote possible shrinkage.)
Both CA125 and PSA are also produced, albeit in smaller amounts, by healthy tissue, complicating efforts to detect cancer at an early stage when the tumor's output of the biomarker is relatively low.
The new mathematical model employs separate equations, each governing the movement of a biomarker from one compartment into the next. Into these equations, one can plug known values such as how fast a particular type of tumor grows, how much of the biomarker a tumor cell of this type sheds per hour and the minimum levels of the biomarker that must be present in the blood for a currently available assay to detect it.
As a test case, Gambhir and Hori chose CA125, a well-studied biomarker shed into blood by ovarian tumors. Ovarian cancer is a notorious example of a condition for which early detection would make a huge difference in survival outcomes.
CA125 is a protein made almost exclusively by ovarian tumor cells. The pharmacokinetics, metabolic fates, typical amounts secreted by an ovarian cell and other properties of CA125 are all well-known, as are ovarian tumors' typical growth rates, making it excellent for "road testing" with Gambhir and Hori's model. CA125 is by no means the ideal biomarker, said Gambhir, just one that can be used to help better understand ideal properties of biomarkers for early ovarian cancer detection.
Applying their equations to CA125, Gambhir and Hori showed that before the currently best available test for CA125 could reliably detect an ovarian tumor, the tumor would need to reach a size of about 1.7 billion cells, or the volume of a cube with about a 2-cm edge. That would take about 10.1 to 12.6 years of development, at typical tumor-growth rates, from the first, single cancer cell.
The model further calculated that a biomarker otherwise equivalent to CA125 but shed only by ovarian tumor cells would allow reliable detection within 7.7 years, when a tumor's size would be that of a tiny cube about one-sixth of an inch high.
In the last decade, many potential new biomarkers for different cancers have been identified. There's no shortage of promising candidates six for lung cancer alone, for example. But validating a biomarker in large clinical trials is a long, expensive process. So it is imperative to determine as efficiently as possible which, among many potential tumor biomarkers, is the best prospective candidate.
"This model could take some of the guesswork out of it," Gambhir said. "It can be applied to all kinds of solid cancers and prospective biomarkers as long as we have enough data on, for instance, how much of it a tumor cell secretes per hour, how long the biomarker can circulate before it's degraded and how quickly tumor cells divide.
"We can tweak one or another variable for instance, whether a biomarker is also made in healthy tissues or just the tumor, or assume we could manage to boost the sensitivity of our blood tests by 10-fold or 100-fold and see how much it advances our ability to detect the tumor earlier on."
There are now new detection technologies capable of detecting biomarkers at concentrations as low as a few hundred molecules per mm (cc) of blood. A couple of years ago, Gambhir and his colleagues reported on one such developing technology: so-called magneto-nanosensors that can detect biomarkers with a 100-fold greater sensitivity than current methods.
Better biomarker detection alone might shrink the time an ovarian tumor can grow before detection to about nine years, said Gambhir.
A second priority is to come up with new and better biomarkers. "It's really important for us to find biomarkers that are made exclusively by tumor cells," he said.
Under the right conditions (a highly sensitive assay measuring levels of a biomarker that is shed only by cancer cells), Gambhir said, the model predicts that a tiny tumor with a volume equivalent to a cube less than one-fifteenth of an inch on a side could be spotted.
Provided by
Stanford University Medical Center
-
Refocusing the boom in biomarker research
Jul 27, 2011 |
not rated yet |
0
-
Researchers identify ovarian cancer biomarkers
Mar 07, 2007 |
not rated yet |
0
-
A faster, simpler test for disease biomarkers
Dec 17, 2007 |
not rated yet |
0
-
The cancer biomarker conundrum: Too many false discoveries
Aug 12, 2010 |
not rated yet |
0
-
Vascular marker of ovarian cancer identified
Sep 23, 2008 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013
-
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013
-
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013
-
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013
-
If you became brain-dead, would you want them to pull the plug?
May 17, 2013
-
MRI bill question
May 15, 2013
- More from Physics Forums - Medical Sciences
More news stories
New fluorescent tools for cancer diagnosis
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer
7 hours ago |
not rated yet |
0
Modulating the immune system to combat metastatic cancer
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer
7 hours ago |
not rated yet |
0
Scientists put bowel cancer under the microscope
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer
10 hours ago |
5 / 5 (1) |
0
Researcher identifies breast cancer fighting hormone
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer
11 hours ago |
5 / 5 (1) |
0
Ground breaking cancer research finds immune system link
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer
11 hours ago |
5 / 5 (3) |
0
Researchers identify first drug targets in childhood genetic tumor disorder
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
Engineered cytomegalovirus protects monkeys from HIV equivalent
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
Hormone levels may provide key to understanding psychological disorders in women
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
Going live: Immune cell activation in multiple sclerosis
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
Driving and hands-free talking lead to spike in errors, study shows
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
Pollen count apps for smartphones are nothing to sneeze at
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.