Cancer biomarker
A cancer biomarker refers to a substance or process that is indicative of the presence of
While numerous challenges exist in translating biomarker research into the clinical space; a number of
Definitions of cancer biomarkers
Organizations and publications vary in their definition of biomarker. In many areas of medicine, biomarkers are limited to proteins identifiable or measurable in the blood or urine. However, the term is often used to cover any molecular, biochemical, physiological, or anatomical property that can be quantified or measured.
The National Cancer Institute (NCI), in particular, defines biomarker as a: “A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule."[18]
In cancer research and medicine, biomarkers are used in three primary ways:[19]
- To help diagnose conditions, as in the case of identifying early stage cancers (diagnostic)
- To forecast how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment (prognostic)
- To predict how well a patient will respond to treatment (predictive)
Role of biomarkers in cancer research and medicine
Uses of biomarkers in cancer medicine
Risk assessment
Cancer biomarkers, particular those associated with genetic
Diagnosis
Cancer biomarkers can also be useful in establishing a specific diagnosis. This is particularly the case when there is a need to determine whether tumors are of primary or metastatic origin. To make this distinction, researchers can screen the chromosomal alterations found on cells located in the primary tumor site against those found in the secondary site. If the alterations match, the secondary tumor can be identified as metastatic; whereas if the alterations differ, the secondary tumor can be identified as a distinct primary tumor.[21] For example, people with tumors have high levels of circulating tumor DNA (ctDNA) due to tumor cells that have gone through apoptosis.[22] This tumor marker can be detected in the blood, saliva, or urine.[17] The possibility of identifying an effective biomarker for early cancer diagnosis has recently been questioned, in light of the high molecular heterogeneity of tumors observed by next-generation sequencing studies.[23]
Prognosis and treatment predictions
Another use of biomarkers in cancer medicine is for disease
Pharmacodynamics and pharmacokinetics
Cancer biomarkers can also be used to determine the most effective treatment regime for a particular person's cancer.
Monitoring treatment response
Cancer biomarkers have also shown utility in monitoring how well a treatment is working over time. Much research is going into this particular area, since successful biomarkers have the potential of providing significant cost reduction in patient care, as the current image-based tests such as CT and MRI for monitoring tumor status are highly costly.[36]
One notable biomarker garnering significant attention is the
Similarly, additional laboratory research has shown that tumor cells undergoing
Recurrence
Cancer biomarkers can also offer value in predicting or monitoring cancer recurrence. The Oncotype DX® breast cancer assay is one such test used to predict the likelihood of breast cancer recurrence. This test is intended for women with early-stage (Stage I or II), node-negative, estrogen receptor-positive (ER+) invasive breast cancer who will be treated with hormone therapy. Oncotype DX looks at a panel of 21 genes in cells taken during tumor biopsy. The results of the test are given in the form of a recurrence score that indicates likelihood of recurrence at 10 years.[39][40]
Uses of biomarkers in cancer research
Developing drug targets
In addition to their use in cancer medicine, biomarkers are often used throughout the cancer drug discovery process. For instance, in the 1960s, researchers discovered the majority of patients with
Surrogate endpoints
Another promising area of biomarker application is in the area of surrogate endpoints. In this application, biomarkers act as stand-ins for the effects of a drug on cancer progression and survival. Ideally, the use of validated biomarkers would prevent patients from having to undergo tumor biopsies and lengthy clinical trials to determine if a new drug worked. In the current standard of care, the metric for determining a drug's effectiveness is to check if it has decreased cancer progression in humans and ultimately whether it prolongs survival. However, successful biomarker surrogates could save substantial time, effort, and money if failing drugs could be eliminated from the development pipeline before being brought to clinical trials.
Some ideal characteristics of surrogate endpoint biomarkers include:[43][44]
- Biomarker should be involved in process that causes the cancer
- Changes in biomarker should correlate with changes in the disease
- Levels of biomarkers should be high enough that they can be measured easily and reliably
- Levels or presence of biomarker should readily distinguish between normal, cancerous, and precancerous tissue
- Effective treatment of the cancer should change the level of the biomarker
- Level of the biomarker should not change spontaneously or in response to other factors not related to the successful treatment of the cancer
Two areas in particular that are receiving attention as surrogate markers include
Types of cancer biomarkers
Molecular cancer biomarkers
Tumor type | Biomarker |
---|---|
Breast | ER/PR (estrogen receptor/progesteron receptor)[52][53] |
HER-2/neu[52][53] | |
Colorectal | EGFR[52][53] |
KRAS[52][54] | |
Gastric | HER-2/neu [52] |
GIST | |
Leukemia/lymphoma | CD20[52][56] |
CD30[52][57] | |
Philadelphia chromosome (BCR/ABL) [52][60][61] | |
UGT1A1 [52][64] | |
Lung | EML4/ALK[52][65][66] |
EGFR [52][53] | |
KRAS [52][53] | |
Melanoma | BRAF[52][66] |
Pancreas | Elevated levels of leucine, isoleucine and valine[67] |
Ovaries | CA-125[68]
|
Other examples of biomarkers:
- Tumor suppressors lost in cancer
- RNA
- Examples:
- Proteins found in body fluids or tissue.
- Examples: CA-125
- Examples:
- Antibodies to cancer antigens
- Examples: Merkel cell polyomavirus[70]
- DNA
Cancer biomarkers without specificity
Not all cancer biomarkers have to be specific to types of cancer. Some biomarkers found in the circulatory system can be used to determine an abnormal growth of cells present in the body. All these types of biomarkers can be identified through diagnostic blood tests, which is one of the main reasons to get regularly health tested. By getting regularly tested, many health issues such as cancer can be discovered at an early stage, preventing many deaths.
The neutrophil-to-lymphocyte ratio has been shown to be a non-specific determinant for many cancers. This ratio focuses on the activity of two components of the immune system that are involved in inflammatory response which is shown to be higher in presence of malignant tumors.[71] Additionally, basic fibroblast growth factor (bFGF) is a protein that is involved in the proliferation of cells. Unfortunately, it has been shown that in the presence of tumors it is highly active which has led to the conclusion that it may help malignant cells reproduce at faster rates.[72] Research has shown that anti-bFGF antibodies can be used to help treat tumors from many origins.[72] Moreover, insulin-like growth factor (IGF-R) is involved in cell proliferation and growth. It has is possible that it is involved in inhibiting apoptosis, programmed cell death due to some defect.[73] Due to this, the levels of IGF-R can be increased when cancer such as breast, prostate, lung, and colorectum is present.[74]
Biomarker | Description | Biosensor used |
---|---|---|
NLR (neutrophil-to-lymphocyte ratio) | Elevates with inflammation caused by cancer[75] | No |
Basic Fibroblast Growth Factor (bFGF) | This level increases when a tumor is present, helps with the fast reproduction of tumor cells[76] | Electrochemical[77] |
Insulin-like Growth Factor (IGF-R) | High activity in cancer cells, help reproduction[78] | Electrochemical Impedance Spectroscopy Sensor[citation needed] |
See also
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