Cancer Biomarkers & Tumor Biology
A clinical overview of circulating biomarkers, driver mutations, actionable genetic fusions, and molecular targets in modern oncology.
Overview
Cancer pathogenesis is driven by genetic mutations and molecular pathway alterations that disrupt normal cell cycle checkpoints and apoptotic mechanisms. Identifying specific molecular biomarkers enables early non-invasive diagnosis, precision risk stratification, and matching patients to targeted kinase inhibitors and immunotherapies.
Major Actionable Biomarkers & Targeted Therapies
| Biomarker |
Biological Role & Mechanism |
Associated Malignancies |
Targeted Therapies |
| EGFR |
Receptor tyrosine kinase controlling cellular growth; activating exon 19 del / L858R mutations drive tumorigenesis. |
Non-Small Cell Lung Cancer (NSCLC), Glioblastoma |
Osimertinib, Erlotinib, Gefitinib, Afatinib |
| HER2 (ERBB2) |
Transmembrane receptor whose amplification causes aggressive cell proliferation and metastatic spread. |
Breast, Gastric, and Gastroesophageal Junction Cancers |
Trastuzumab, Pertuzumab, Trastuzumab Deruxtecan (T-DXd) |
| KRAS |
GTPase transducer in the MAPK pathway; G12C/G12D point mutations lock the protein in an active signaling state. |
Colorectal, Pancreatic Ductal, and Non-Small Cell Lung Cancers |
Sotorasib, Adagrasib, emerging pan-KRAS inhibitors |
| BRAF |
Serine/threonine kinase downstream of KRAS; V600E mutation triggers constitutive MEK/ERK phosphorylation. |
Melanoma, Colorectal, Anaplastic Thyroid Cancers |
Dabrafenib + Trametinib, Encorafenib + Cetuximab |
| ALK Fusions |
Chromosomal inversions (e.g., EML4-ALK) producing constitutively active chimeric receptor kinases. |
Non-Small Cell Lung Cancer, ALCL Lymphoma |
Alectinib, Brigatinib, Lorlatinib, Crizotinib |
| BRCA1 & BRCA2 |
Essential tumor suppressors coordinating homologous recombination DNA double-strand break repair. |
Hereditary Breast, Ovarian, Pancreatic, and Prostate Cancers |
PARP Inhibitors: Olaparib, Rucaparib, Niraparib, Talazoparib |
| NTRK 1/2/3 Fusions |
Agonist-independent neurotrophin receptor kinase fusions driving oncogenesis across diverse tumor histologies. |
Secretory Breast Carcinoma, Infantile Fibrosarcoma, Thyroid Cancers |
Larotrectinib, Entrectinib |
Liquid Biopsy & Circulating Biomarkers
1. Circulating Tumor DNA (ctDNA)
ctDNA comprises short fragmented DNA strands shed into peripheral circulation by apoptotic and necrotic tumor cells.
- Clinical Applications: Non-invasive molecular genotyping, monitoring therapeutic response, detecting Minimal Residual Disease (MRD), and identifying emerging resistance mutations months before radiographical detection.
2. Circulating Tumor Cells (CTCs)
Intact neoplastic cells that detach from primary or metastatic tumor deposits and enter the bloodstream.
- Clinical Applications: Evaluating metastatic seeding risk, longitudinal disease monitoring, and functional single-cell pharmacodynamic testing.
Predictive Immunotherapy Biomarkers
1. PD-L1 (Programmed Death-Ligand 1)
Expressed on tumor cells and tumor-infiltrating immune cells to engage PD-1 on cytotoxic T-cells, suppressing anti-tumor immunity.
- Clinical Application: Guides monotherapy vs. chemo-immunotherapy regimens with checkpoint inhibitors (Pembrolizumab, Nivolumab, Atezolizumab).
2. Microsatellite Instability (MSI-H / dMMR)
Hypermutability resulting from defective DNA mismatch repair enzymes (MLH1, MSH2, MSH6, PMS2), generating high neoantigen loads.
- Clinical Application: FDA tumor-agnostic indication for immune checkpoint blockade.
3. Tumor Mutational Burden (TMB-High)
Quantification of somatic nonsynonymous mutations per megabase (≥10 mut/Mb), correlating with elevated immunogenicity and checkpoint inhibitor responsiveness.
Comprehensive genomic testing identifies actionable mutations early in the diagnostic pathway, ensuring each patient receives the most effective targeted or immunotherapy regimen available.
