The Role of Biomarkers
In many tumor types, biomarkers represent an important paradigm shift in cancer
care. These biologic indicators are increasingly being used to help physicians screen,
detect, and diagnose patients; they help in prognostic evaluation, treatment response,
and disease recurrence monitoring.1
There are many different categories of biomarkers that all have different
roles. Four common categories are found below:2
Detection biomarkers
Detection biomarkers aid in identifying cancers. One example is prostate-specific
antigen (PSA), a marker that has been used for many years in early prostate cancer
detection.1
Diagnostic biomarkers
Diagnostic biomarkers normally signal the presence of a cancer or the risk of developing
one. One common example is the breast cancer type 1 and type 2 susceptibility protein
(BRCA 1 and 2), a human tumor suppressor gene that, when mutated, is indicative
of a woman's potential risk of developing breast cancer.1
Prognostic biomarkers
Prognostic biomarkers give an indication of long-term outcomes, regardless of specific
therapy.3 Prognostic biomarkers also may provide
information on disease recurrence, and may correlate with clinical outcomes.
Predictive biomarkers
Predictive biomarkers characterize a patient's disease in order to help determine
if the patient's cancer might respond to a specific treatment.
4
Identification of predictive biomarkers has made selecting appropriate and potent
treatment regimens possible for patients with various tumor types. These include:
- The Human Epidermal Growth Factor Receptor 2 (HER-2): a critical
predictor of response to anti-HER-2 therapy in patients with breast cancer. HER-2
is over-expressed in about 25% to 30% of breast cancers, and helps clinicians predict
the performance of therapy early and with a high degree of certainty.5
- C-KIT: the presence of certain mutations is an indicator of treatment
response in patients with gastrointestinal stromal tumors (GIST).6
- KRAS: a gene that is part of the signaling pathway of EGFR. A
mutated KRAS gene allows the signaling pathway to remain activated, even when EGFR
inhibitors have blocked the pathway. In metastatic colorectal cancer, KRAS status
helps identify patients who may or may not be candidates for anti-EGFR therapy.7
Biomarkers may play important roles in many aspects of cancer management: they may
be utilized as tools for drug discovery,8 as pharmacodynamic
(PD) markers for drug efficacy both preclinically and in early-phase trials,8 and as surrogate endpoints for disease progression
in late-phase trials.8 Biomarkers may likely have
a role in the development of future treatments, as well.8
Emerging Biomarkers The adoption of personalized
medicine has led to increased efforts to identify new biomarkers across tumor types.
In addition to well-established biomarkers such as KRAS and EGFR in colorectal and
lung cancer and HER-2 and ER/PR in breast cancer, many emerging biomarkers are being
investigated in multiple tumor types. Some have started showing promising data,
but they will have to go through many steps in the validation process, which might
take many years of research.