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Improved blood tests for cancer screening: general or specific?

Cree IA - BMC Cancer (2011)

Bottom Line: Recent developments suggest the possibility of blood-based screening for multiple tumour types.While the assays required for each step exist, they have not been used in this way.Recent experience of screening for breast, cervical and ovarian cancers suggest that there is likely to be widespread acceptance of such a strategy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Translational Oncology Research Centre, Queen Alexandra Hospital, Southwick Hill, Portsmouth, PO6 3LY, UK. ian.cree@porthosp.nhs.uk

ABSTRACT
Diagnosis of cancer at an early stage leads to improved survival. However, most current blood tests detect single biomarkers that are of limited suitability for screening, and existing screening programmes look only for cancers of one particular type. A new approach is needed. Recent developments suggest the possibility of blood-based screening for multiple tumour types. It may be feasible to develop a high-sensitivity general screen for cancer using multiple proteins and nucleic acids present in the blood of cancer patients, based on the biological characteristics of cancer. Positive samples in the general screen would be submitted automatically for secondary screening using tests to help define the likelihood of cancer and provide some indication of its type. Only those at high risk would be referred for further clinical assessment to permit early treatment and mitigate potential overdiagnosis. While the assays required for each step exist, they have not been used in this way. Recent experience of screening for breast, cervical and ovarian cancers suggest that there is likely to be widespread acceptance of such a strategy.

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Related in: MedlinePlus

Tumour biomarkers in blood reflect the major processes resulting in tumour formation by cancer cells and the host reaction.
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Figure 1: Tumour biomarkers in blood reflect the major processes resulting in tumour formation by cancer cells and the host reaction.

Mentions: Despite its history, blood-based screening for cancer remains attractive, as it could provide inexpensive testing that would arguably be more acceptable to patients and easily incorporated into an annual checkup, which might include cholesterol and other assays of general health. This idea was judged too risky to be funded when put forward in 2005, but six years later, the recent review along similar lines by Hanash et al. [9] has shown how fast the necessary underlying science is advancing. There is no doubt that cancers have characteristics that could be detected by performing blood-based screening tests (Figure 1). In 2000, Hanahan and Weinberg [10] published their seminal paper describing the Hallmarks of Cancer, and many authors since then have described changes in blood related to these characteristics. Hanahan and Weinberg pointed out that cancer cell growth is the result of self-sufficiency in growth signals and insensitivity to antigrowth signals. Such signals are often mediated by growth factors, which may rise above normal levels in peripheral blood [11]. Growth has consequences: Even in the early stages there may be detectable metabolic changes [12,13], though these often lack specificity [14]. Cancer cells also upregulate mechanisms that allow them to evade apoptosis, and some of these also cause the release of cytokines into blood [15,16]. Many tumours also have increased cell turnover: They grow because they divide faster than they die, but there is still increased cell death by apoptosis or necrosis. This overloads the local clearance mechanisms for dead cells in tissues and leads to the appearance of partly caspase-digested proteins and DNA fragments in peripheral blood [17-19]. The amount of DNA present is increased and may contain mutations or altered methylation [20-23]. More recently, the presence of RNA, particularly in the form of miRNA [24,25] and exosomes [25-27] derived from cancer cells in blood, has opened up new avenues of research. Tumours require the ability to make new blood vessels, and many therefore produce proangiogenic factors, which can be found in blood [28,29]. They also increase the number of endothelial cell precursors in blood [29]. Immunological abnormalities are common in many cancer patients, with the appearance of autoantibodies to p53 and other intracellular antigens [30]. Finally, malignant cells invade and metastasise. While few metastatic cells survive and grow, their presence can be detected in blood by using sensitive assays [31].


Improved blood tests for cancer screening: general or specific?

Cree IA - BMC Cancer (2011)

Tumour biomarkers in blood reflect the major processes resulting in tumour formation by cancer cells and the host reaction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285105&req=5

Figure 1: Tumour biomarkers in blood reflect the major processes resulting in tumour formation by cancer cells and the host reaction.
Mentions: Despite its history, blood-based screening for cancer remains attractive, as it could provide inexpensive testing that would arguably be more acceptable to patients and easily incorporated into an annual checkup, which might include cholesterol and other assays of general health. This idea was judged too risky to be funded when put forward in 2005, but six years later, the recent review along similar lines by Hanash et al. [9] has shown how fast the necessary underlying science is advancing. There is no doubt that cancers have characteristics that could be detected by performing blood-based screening tests (Figure 1). In 2000, Hanahan and Weinberg [10] published their seminal paper describing the Hallmarks of Cancer, and many authors since then have described changes in blood related to these characteristics. Hanahan and Weinberg pointed out that cancer cell growth is the result of self-sufficiency in growth signals and insensitivity to antigrowth signals. Such signals are often mediated by growth factors, which may rise above normal levels in peripheral blood [11]. Growth has consequences: Even in the early stages there may be detectable metabolic changes [12,13], though these often lack specificity [14]. Cancer cells also upregulate mechanisms that allow them to evade apoptosis, and some of these also cause the release of cytokines into blood [15,16]. Many tumours also have increased cell turnover: They grow because they divide faster than they die, but there is still increased cell death by apoptosis or necrosis. This overloads the local clearance mechanisms for dead cells in tissues and leads to the appearance of partly caspase-digested proteins and DNA fragments in peripheral blood [17-19]. The amount of DNA present is increased and may contain mutations or altered methylation [20-23]. More recently, the presence of RNA, particularly in the form of miRNA [24,25] and exosomes [25-27] derived from cancer cells in blood, has opened up new avenues of research. Tumours require the ability to make new blood vessels, and many therefore produce proangiogenic factors, which can be found in blood [28,29]. They also increase the number of endothelial cell precursors in blood [29]. Immunological abnormalities are common in many cancer patients, with the appearance of autoantibodies to p53 and other intracellular antigens [30]. Finally, malignant cells invade and metastasise. While few metastatic cells survive and grow, their presence can be detected in blood by using sensitive assays [31].

Bottom Line: Recent developments suggest the possibility of blood-based screening for multiple tumour types.While the assays required for each step exist, they have not been used in this way.Recent experience of screening for breast, cervical and ovarian cancers suggest that there is likely to be widespread acceptance of such a strategy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Translational Oncology Research Centre, Queen Alexandra Hospital, Southwick Hill, Portsmouth, PO6 3LY, UK. ian.cree@porthosp.nhs.uk

ABSTRACT
Diagnosis of cancer at an early stage leads to improved survival. However, most current blood tests detect single biomarkers that are of limited suitability for screening, and existing screening programmes look only for cancers of one particular type. A new approach is needed. Recent developments suggest the possibility of blood-based screening for multiple tumour types. It may be feasible to develop a high-sensitivity general screen for cancer using multiple proteins and nucleic acids present in the blood of cancer patients, based on the biological characteristics of cancer. Positive samples in the general screen would be submitted automatically for secondary screening using tests to help define the likelihood of cancer and provide some indication of its type. Only those at high risk would be referred for further clinical assessment to permit early treatment and mitigate potential overdiagnosis. While the assays required for each step exist, they have not been used in this way. Recent experience of screening for breast, cervical and ovarian cancers suggest that there is likely to be widespread acceptance of such a strategy.

Show MeSH
Related in: MedlinePlus