The number of cancer biomarkers with associated targeted therapies continues to increase. We are at a place now with NGS-based comprehensive genomic profiling where one biopsy, one test, and one report can lead to improved outcomes for cancer patients, thereby advancing precision medicine and improving patient health and wellness.1-2
There are several key considerations when evaluating a cancer biomarker test to aid with therapy selection.
Conventional testing with techniques like FISH, PCR and IHC are insufficient to assess all relevant cancer biomarkers and preserve precious tissue samples. Individual sequential biomarker tests are common; however, they have some disadvantages. First, these tests require a significant amount of biopsy sample that’s not always accessible. Second, these single gene tests have limited content and may miss the opportunity to identify a positive biomarker.
A next-generation sequencing (NGS)-based biomarker test can analyze hundreds of clinically actionable cancer biomarkers simultaneously. This additional data provides more opportunity to match patients with appropriate molecular treatment regime. A single NGS-based biomarker test can replace multiple single-gene tests or small hotspot panels.4-7
If tissue biopsies are unavailable, comprehensive genomic profiling (CGP) from liquid biopsy may provide helpful information about a tumor's genomic make-up. This can decrease the need to rebiopsy and save precious time in the care continuum.8
In addition to genes specifically involved in immune pathways, associated biomarkers have emerged that rely upon assessment of numerous genomic loci, such as tumor mutational burden (TMB) and microsatellite instability (MSI).
Associated with the increasing number of discovered fusion events is the number of clinically actionable cancer biomarkers. Examples of clinically actionable gene fusions include NTRK and RET gene fusions.
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HRD (homologous recombination deficiency) is a phenotype used to describe loss of function in the HRR (homologous recombination repair) pathway. When this occurs, cells are unable to repair double-stranded DNA breaks, leading to tumorigenesis.
HRD can be measured by "cause," such as a BRCA mutation or by "consequence" in the form of genomic scarring. NGS technology can assess both causal genes and genomic scarring.
There are multiple types of mutations that are associated with cancer-related genes, such as single-nucleotide variants (SNVs), insertions and deletions (indels), and copy-number variants (CNVs).
Traditionally these specific biomarkers have been analyzed with single-gene tests, but as the number of biomarkers increases for each cancer type, more labs have turned to NGS methods that can analyze numerous genes and variant types in a single assay.
Comprehensive genomic profiling (CGP) consolidates hundreds of cancer-related biomarkers into a single assay, eliminating the need for sequential testing. CGP can detect biomarkers at nucleotide-level resolution and typically comprises all major genomic variant classes (SNVs, indels, CNVs, fusions, and splice variants), as well as large genomic signatures (TMB and MSI), maximizing the ability to find clinically actionable alterations.
Learn more about CGPMaximize identification of molecularly matched therapies.
CGP provides tumor-agnostic testing for hundreds of relevant cancer biomarkers, per guidelines, in a single assay, potentially offering significant savings in sample, time, and cost.
Pan-Cancer Biomarkers NTRK1 NTRK2 NTRK3 MSI TMB RET BRAF | ||||||||
---|---|---|---|---|---|---|---|---|
Lung | Melanoma | Colon | Ovarian | Breast | Gastric | Bladder | Sarcoma | |
AKT1 | BRAF | AKT1 | BRAF | AKT1 | BRAF | MSH5 | ALK | |
ALK | CTNNB1 | BRAF | BRCA1 | AR | KIT | PMS2 | APC | |
BRAF | GNA11 | HRAS | BRCA2 | BRCA1 | KRAS | TSC1 | BRAF | |
DDR2 | GNAQ | KRAS | KRAS | BRCA2 | MET | CDK4 | ||
EGFR | KIT | MET | PDGFRA | ERBB2 | MLH1 | CTNNB1 | ||
ERBB2 | MAP2K1 | MLH1 | FOXL2 | FGFR1 | PDGFRA | ETV6 | ||
FGFR1 | NF1 | MSH2 | TP53 | FGFR2 | TP53 | EWSR1 | ||
FGFR3 | NRAS | MSH6 | PIK3CA | FOXO1 | ||||
KRAS | PDGFRA | NRAS | PTEN | GLI1 | ||||
MAP2K1 | PIK3CA | PIK3CA | KJT | |||||
MET | PTEN | PMS2 | MDM2 | |||||
NRAS | TP53 | PTEN | MYOD1 | |||||
PIK3CA | SMAD4 | NAB2 | ||||||
PTEN | TP53 | NF1 | ||||||
RET | PAX3 | |||||||
TP53 | PAX7 | |||||||
PDGFRA | ||||||||
PDGFRB | ||||||||
SDHB | ||||||||
SDHC | ||||||||
SMARCB1 | ||||||||
TFE3 | ||||||||
WT1 |
The genes shown here are not an exhaustive list.
These walk-away automation methods for Illumina kits eliminate the need to develop your own method and can help you reduce hands-on time and minimize errors.
Dr. Sandip Patel of UCSD provides an overview of biomarker-guided therapies for thyroid cancer and non-small cell lung cancer (NSCLC) and discusses key emerging biomarkers for these indications along with their supporting evidence.
Phil Febbo, MD discusses the benefits of CGP and how it’s becoming a new standard of care in oncology.
Dr Eliezer Van Allen highlights how NGS can identify biomarkers of response and resistance to immunotherapy, and can determine how cancers develop resistance to immune checkpoint blockade.
Scientists discuss the advantages of comprehensive NGS-based panels for biomarker discovery.
Phil Febbo, MD discusses the benefits of CGP and how it’s becoming a new standard of care in oncology.
NGS methods enable efficient assessment of tumor mutational burden and identification of neoantigens.
NGS methods enable efficient assessment of tumor mutational burden and identification of neoantigens.
NGS and microarray technologies can detect altered DNA methylation patterns and other epigenetic modifications that regulate cancer progression.