Introduction
Strategies for molecular characterization of patients
SNP Genotyping
Next generation sequencing
Biomarkers for successful drug development
Predictive biomarkers
Pharmacodynamics, pharmacokinetics and pharmacogenomics
Intermediate endpoint biomarkers
Proteomics and metabolomics
Modern functional imaging biomarkers
Lessons learnt from successes in drug development
Biomarker | Drug | Drug action | Cancer type (Survival benefit) |
---|---|---|---|
ALK
| Ceritinib | Tyrosine kinase inhibitor of ALK | Lung cancer |
Crizotinib | Tyrosine kinase inhibitor of ALK | Lung cancer | |
BRAF (V600E)
| Dabrafenib | Inhibits B-RAF protein | Melanoma |
Trametinib | Inhibits MEK1 and MEK2 growth factor-mediated signaling | Melanoma | |
Vemurafenib | Small molecule inhibitor of BRAF (V600E) kinase | Melanoma | |
CTLA-4
| Ipilimumab | Monoclonal antibody directed against CTLA-4, enhancing T-cell activation | Melanoma |
EGFR
| Afatinib | Irreversibly inhibits EGFR, HER2, HER4, mutant EGFR (exon 19, 21) | Lung cancer |
Cetuximab | Recombinant, chimeric, monoclonal antibody directed against EGFR | Colorectal cancer, SCCHN** | |
Erlotinib | Reversible tyrosine kinase inhibitor of EGFR | Lung cancer, Pancreatic cancer | |
Gefinitib | Tyrosine kinase inhibitor of EGFR | Lung cancer | |
Panitumumab | Humanized monoclonal antibody directed against EGFR | Colorectal cancer | |
HER2
| Lapatinib | Reversible tyrosine kinase inhibitor of EGFR, HER2 | Breast cancer |
Pertuzumab | Recombinant, humanized, monoclonal antibody preventing HER2 dimerization | Breast cancer | |
Trastuzumab | Recombinant, humanized, monoclonal antibody directed against HER2 | Breast cancer, Gastric cancer | |
Trastuzumab-mertansine (T-DM1) | Antibody-drug conjugate consisting of trastuzumab conjugated to DM1, which binds tubulin and disrupts microtubule assembly/disassembly dynamics | Breast cancer | |
KIT
| Imatinib | Tyrosine kinase inhibitor of c-kit | GIST*** |
Sunitinib | Tyrosine kinase inhibitor of VEGFR2, PDGFRb and c-KIT | GIST*** | |
MEK
| Trametinib | MEK1/2 inhibitor | Melanoma |