[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Precision oncology: driver mutations, biomarker testing and liquid biopsy # Precision oncology: driver mutations, biomarker testing and liquid biopsy Testing a tumour's genes can show which targeted drug may work. Tumours change over time, so testing may need repeating. Updated Nov 12, 2026 On this page - The basics Key points - Cancer evolution and driver mutations - Oncogene addiction and synthetic lethality - Biomarker testing in practice - Tumour heterogeneity - Liquid biopsy and circulating tumour DNA - How resistance to targeted drugs develops - Memory aid - Example drugs - Study Test yourself - Connections Connections Cancers grow from cells that have collected mutations over years. A few of these, the drivers, give the tumour its growth advantage, and many tumours stay dependent on one of them. Precision oncology tests the tumour (in tissue or in blood) for such targets and matches drugs to them. Because tumours are mixtures of evolving subclones, a single test is a snapshot, and resistance often appears as a new mutation. ## Key points - Driver mutations give a growth advantage; passenger mutations come along for the ride and are not useful targets. - Oncogene addiction: many tumours depend on one overactive pathway, so blocking it (imatinib for BCR-ABL, osimertinib for EGFR) can collapse the tumour. - Synthetic lethality: cancer cells that already lack one DNA-repair route (BRCA1/2) die when a second route is blocked (PARP inhibitors), while normal cells survive. - Companion diagnostics are tests approved together with a specific drug to select patients. - Liquid biopsy measures circulating tumour DNA (ctDNA) in blood; it can avoid a tissue biopsy and track resistance mutations over time. - Tumour heterogeneity means one biopsy may miss important subclones. ## Cancer evolution and driver mutations By the time a cancer is diagnosed, it has evolved for years from a few precursor cells. Each division can add mutations, so the primary tumour and its metastases contain related but different subpopulations. Among the many changes, drivers are those that activate oncogenes (such as EGFR, ALK fusions, BRAF V600E, KRAS, HER2 amplification) or disable tumour suppressors and DNA repair (such as TP53 or BRCA1/2). Targeted drug discovery starts from these drivers: find the altered protein, then design a small molecule or antibody against it. ## Oncogene addiction and synthetic lethality - Oncogene addiction: chronic myeloid leukaemia depends on the BCR-ABL kinase, and imatinib produces deep responses; imatinib also controls gastrointestinal stromal tumours driven by mutant KIT. - EGFR-mutant lung cancer responds to EGFR inhibitors such as osimertinib; HER2-amplified breast cancer responds to trastuzumab. - Synthetic lethality: losing either of two repair pathways is survivable, losing both is lethal. BRCA-mutant tumours lack homologous recombination; PARP inhibitors (olaparib) remove the backup pathway, so tumour cells die. - Basket trials group patients by their tumour's target rather than its organ, leading to tissue-agnostic approvals such as pembrolizumab for MSI-high or mismatch-repair-deficient tumours and larotrectinib for NTRK fusions. ## Biomarker testing in practice Biomarker tests look for genes, proteins or other features of the tumour that predict benefit or lack of benefit. Tumour (somatic) testing is different from inherited (germline) testing; if a tumour test reveals a possible inherited change, genetic counselling follows. Some tests look at one marker; multigene panels and broader sequencing look at many at once. Tumour mutational burden counts mutations and can help predict response to some immunotherapies. - Predictive markers for therapy: hormone receptors and HER2 in breast cancer; EGFR, ALK and other drivers in lung cancer; BRCA and other repair genes for PARP inhibitors. - Negative selection: a KRAS-mutated colorectal tumour is not expected to benefit from anti-EGFR antibodies such as cetuximab. - Results can be actionable (a matched approved drug or a trial), show that a drug is unlikely to work, or be variants of unknown significance that do not guide treatment. ## Tumour heterogeneity Different parts of a tumour, and different metastases, may carry different mutations. A small biopsy from one site can miss a subclone that later drives resistance, and lesions may respond unevenly to the same drug. Biomarkers also change over time, especially under treatment pressure, so testing may be repeated when the cancer progresses or returns. ## Liquid biopsy and circulating tumour DNA Dying tumour cells release fragments of DNA into the blood. Sequencing this circulating tumour DNA (ctDNA) can detect targetable mutations when a tissue biopsy is unsafe or insufficient; a blood test for EGFR mutations, for example, is used to select lung cancer patients for EGFR inhibitors. Repeated samples show how subclones rise and fall: during anti-oestrogen therapy of breast cancer, mutant oestrogen receptor (ESR1) in ctDNA can appear before clinical resistance. ## How resistance to targeted drugs develops - The target itself mutates so the drug no longer binds (for example, new kinase-domain mutations). - The tumour switches to another growth pathway that bypasses the target. - A pre-existing resistant subclone expands under treatment. - Responses: next-generation inhibitors, drug combinations, and repeat biomarker testing at progression. ## Memory aid Drive, Depend, Detect: find the Driver, exploit the Dependence, Detect change over time with repeat or liquid biopsy. ## Test yourself Think of the answer, then tap the question to see it. ## What is oncogene addiction, and which drug illustrates it in chronic myeloid leukaemia? A tumour's dependence on one overactive pathway for survival; imatinib blocks the BCR-ABL kinase that drives chronic myeloid leukaemia. ## How do PARP inhibitors exploit synthetic lethality in BRCA-mutant cancers? BRCA-mutant cells already lack homologous recombination repair; PARP inhibition removes a backup pathway, so the tumour cells die while normal cells cope. ## What is a liquid biopsy? Analysis of circulating tumour DNA in a blood sample to find or follow tumour mutations without a tissue biopsy. ## Why can a single tumour biopsy give misleading guidance for targeted therapy? Tumours are mixtures of evolving subclones; one sample may miss a subclone with a different or resistant mutation, and biomarkers change over time. ## What is a companion diagnostic? A test approved together with a specific drug to identify the patients likely to benefit from it. [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/precision-oncology-driver-mutations-biomarker-testing-and-liquid-biopsy/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Imatinib](https://durgical.com/en/pharmacology/imatinib/) - [Osimertinib](https://durgical.com/en/pharmacology/osimertinib/) - [Erlotinib](https://durgical.com/en/pharmacology/erlotinib/) - [Crizotinib](https://durgical.com/en/pharmacology/crizotinib/) - [Vemurafenib](https://durgical.com/en/pharmacology/vemurafenib/) - [Dabrafenib](https://durgical.com/en/pharmacology/dabrafenib/) - [Sotorasib](https://durgical.com/en/pharmacology/sotorasib/) - [Trastuzumab](https://durgical.com/en/pharmacology/trastuzumab/) - [Cetuximab](https://durgical.com/en/pharmacology/cetuximab/) - [Olaparib](https://durgical.com/en/pharmacology/olaparib/) - [Larotrectinib](https://durgical.com/en/pharmacology/larotrectinib/) - [Pembrolizumab](https://durgical.com/en/pharmacology/pembrolizumab/) - [Elacestrant](https://durgical.com/en/pharmacology/elacestrant/) ## Connections ## Related classes 9 - [Kinase inhibitors (targeted oncology)](https://durgical.com/en/pharmacology/classes/kinase-inhibitors/) - [PARP inhibitors](https://durgical.com/en/pharmacology/classes/parp-inhibitors/) - [ALK and ROS1 inhibitors](https://durgical.com/en/pharmacology/classes/alk-and-ros1-inhibitors/) - [BRAF and MEK inhibitors](https://durgical.com/en/pharmacology/classes/braf-and-mek-inhibitors/) - [KRAS G12C inhibitors](https://durgical.com/en/pharmacology/classes/kras-g12c-inhibitors/) - [TRK and RET inhibitors (tumour-agnostic kinase inhibitors)](https://durgical.com/en/pharmacology/classes/trk-and-ret-inhibitors/) - [HER2 tyrosine kinase inhibitors](https://durgical.com/en/pharmacology/classes/her2-tyrosine-kinase-inhibitors/) - [Immune checkpoint inhibitors](https://durgical.com/en/pharmacology/classes/immune-checkpoint-inhibitors/) - [Antineoplastic monoclonal antibodies](https://durgical.com/en/pharmacology/classes/antineoplastic-monoclonal-antibodies/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Biomarker Testing for Cancer Treatment](https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment) (U.S. National Cancer Institute, 2026); [Targeted Therapy to Treat Cancer](https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies) (U.S. National Cancer Institute, 2026); [Olaparib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/olaparib) (U.S. National Cancer Institute, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/precision-oncology-driver-mutations-biomarker-testing-and-liquid-biopsy/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/precision-oncology-driver-mutations-biomarker-testing-and-liquid-biopsy/