Actionable Cancer Protein or Gene Mutation Biomarkers Are Present in Only A Minority of Cancers

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During the 1980s-1990s there was intense research to determine if there were certain cancers that expressed specific proteins that would provide actionable targeted chemotherapies that would improve patient outcomes. The most notable early examples were the expression of estrogen and progesterone receptors on breast cancer in which hormonal manipulation would improve treatment outcomes. Subsequently, identification of Her-2 in breast cancer led to improved outcomes with the biologic, Herceptin. Other actionable protein biomarkers were identified for other cancers such as EGRF mutations in lung cancer that is currently treated with tyrosine kinase inhibitors. More lately, biomarkers such as PD-L1 is a biomarker for immunotherapy. However, there are shortcoming of these biomarkers. First, biomarkers are frequently present in a minority of cancers. Second, even the presence of these actionable biomarkers do not result in absolute cures when treated with targeted treatments.

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Once DNA sequencing technology dramatically improved and became cheaper, coupled with the aforementioned shortcomings of biomarkers, cancer research transitioned to sequencing part or all of the entire cancer genome to identify gene mutations that could predict clinical outcomes and actionable treatments. Yet, this approach has not led to the holy grail in oncology.

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