Oncogenic driver identification |
BRAF V600E, KIT, EGFR, ERBB2, FGFR3, PIK3CA, AKT1, TSC1, ROS1 mutations, ERBB2 amplifications, ALK translocations |
WES, or targeted sequencing of tumor DNA or ctDNA |
Is it useful to sequence large panels of genes vs actionable drivers? |
Characterization of resistance |
EGFR T790M, ESR1 mutations |
WES, or targeted sequencing of tumor DNA or ctDNA |
Is it useful to detect genetic mechanisms of resistance earlier, using ctDNA? |
Identification of patients sensitive to immunotherapy |
Mutational burden; neoantigens; Gene expression profiles |
WES, or targeted (large panel) sequencing of tumor DNA; RNA‐Seq of tumor |
Can identification of mutational process and clonality improve prediction based on mutational burden? Can personalized cancer vaccines boost responses to immune checkpoint inhibitors? Can gene expression signatures identify immune‐responsive tumors? |
Germline mutations |
BRCA1, BRCA2, PTEN, TSC1, CDH1
|
WGS or WES of normal DNA |
Should the number of patients screened for germline mutations be expanded? Is it useful to interrogate a broad panel of genes ? |
Quantification of intratumor heterogeneity |
none |
Whole exome sequencing of multiple tumor sites and metastatic lesions, or plasma |
Is ITH associated with resistance to therapy and worse outcome? Is it targetable? |
Quantification of pathway activation |
ER, AR, mTOR, and CDK4 signatures |
RNA‐Seq of tumors |
Can gene expression signatures identify responsive patients for targeted therapies? |
Cancer screening |
none |
Ultradeep sequencing of plasma |
Can ultradeep sequencing on ctDNA identify some cancers early? Is it useful? |
Regulatory approval |
none |
Any |
How can clinical validity of NGS tests be established for previously approved biomarkers? What level of evidence is required for biomarkers that are rare in an indication? How will approval be maintained as the field advances? |