Precision medicine has fundamentally changed how cancer is treated. Rather than selecting therapy based solely on where a tumor originates, oncologists increasingly make treatment decisions based on a tumor's molecular characteristics — the specific mutations, gene fusions, protein expressions, and pathway alterations that drive each individual cancer. This shift from anatomy-based to biology-based treatment has produced some of the most dramatic therapeutic advances in oncology history.
The Foundation: Comprehensive Genomic Profiling
Comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) analyzes hundreds of cancer-related genes simultaneously from a single tumor sample. This technology has replaced sequential single-gene testing in most settings, as it is both more efficient and more comprehensive. CGP identifies point mutations, insertions/deletions, copy number alterations, and gene fusions — any of which may be therapeutically relevant.
The clinical utility of CGP varies by tumor type. In non-small cell lung cancer, CGP identifies targetable alterations in 60-70% of adenocarcinomas. In biliary tract cancer, 40-50% harbor actionable targets. In pancreatic cancer, approximately 25% have actionable findings. Current NCCN guidelines recommend CGP at diagnosis for most advanced solid tumors.
Tumor-Agnostic Approvals: Treating the Mutation, Not the Organ
One of the most paradigm-shifting developments in precision oncology has been tumor-agnostic FDA approvals — drugs approved for any solid tumor harboring a specific molecular alteration, regardless of the cancer's anatomic origin. Pembrolizumab for MSI-H/dMMR tumors was the first such approval in 2017, followed by larotrectinib and entrectinib for NTRK fusion-positive tumors. These approvals validated the principle that molecular biology can be more important than tissue of origin in determining treatment response.
Key Targetable Alterations Across Tumor Types
The landscape of targetable alterations continues to expand. EGFR mutations in lung cancer, HER2 amplification in breast and gastric cancer, BRAF V600E across melanoma, thyroid, and colorectal cancer, FGFR alterations in bladder and biliary tract cancer, and IDH mutations in AML and cholangiocarcinoma — each has FDA-approved targeted therapies.
Perhaps the most exciting frontier is the targeting of KRAS, long considered the most important undruggable oncogene. KRAS G12C inhibitors are now approved for lung cancer, with KRAS G12D inhibitors in development for pancreatic cancer — the malignancy most frequently driven by KRAS mutations.
Liquid Biopsy: Non-Invasive Molecular Profiling
Liquid biopsy — the analysis of circulating tumor DNA (ctDNA) from a simple blood draw — has emerged as a complement to tissue-based profiling. Liquid biopsy can identify targetable mutations when tissue is insufficient, detect resistance mutations at progression, and monitor treatment response in real time. In lung cancer, liquid biopsy for EGFR mutations is now a standard component of molecular workup.
PipelineEvidence documents all FDA-approved targeted therapies and the biomarkers that guide their use. Our molecular biology sections for each tumor type detail the key genomic alterations and their therapeutic implications. Explore our therapy database filtered by drug class to see the full targeted therapy landscape.