Molecular / biomarker testing explained — EGFR, ALK, ROS1, KRAS, PD-L1

EGFR and ALK are two different changes in the cancer's genes, and a lung cancer usually has one or the other, not both. EGFR is a mutation — a small change in the EGFR gene — and it is one of the most common targetable changes, especially in non-smokers and adenocarcinoma. ALK is a rearrangement, where part of the ALK gene joins another gene to drive the cancer. Both can be matched to targeted tablets, but they respond to different drugs: an EGFR-positive cancer is treated with an EGFR inhibitor, and an ALK-positive cancer with an ALK inhibitor. That is exactly why biomarker testing matters — it tells your team which treatment is likely to work for your specific cancer.

Molecular testing, also called biomarker testing or a lung cancer mutation test, examines the cancer tissue for specific gene changes and proteins. Instead of only looking at how the cells appear under a microscope, the laboratory reads the cancer's own biology. Common targets include EGFR, ALK, ROS1, KRAS and PD-L1. The purpose is to match the cancer to the most effective treatment, because two lung cancers that look the same can behave differently depending on their genetics. It is most useful in non-small cell lung cancer, particularly adenocarcinoma, and it sits alongside your biopsy and staging rather than replacing them.

Usually not. In most cases biomarker testing is done on the same tissue that was taken to confirm your diagnosis, so a separate procedure is not needed. Sometimes, if the original sample is very small, your team may discuss taking a little more tissue to complete the panel. When obtaining more tissue is difficult, a blood test — sometimes called a liquid biopsy — can look for the same gene changes circulating in the blood. Your oncologist will explain which approach suits your situation and why, so nothing happens without your understanding.

PD-L1 is a protein on the surface of some cancer cells, and it is measured as a percentage rather than simply present or absent. A higher PD-L1 level suggests that immunotherapy — treatment that helps your own immune system attack the cancer — is more likely to help. The result often guides whether immunotherapy is used on its own or combined with chemotherapy. A low or negative PD-L1 result does not rule immunotherapy out completely, but it is one of several factors your tumour board weighs. Your doctor will explain what your specific percentage means for your treatment choices.

It usually takes longer than imaging because the tissue must be examined carefully. Some single-marker tests come back within a few days, while a broad next-generation sequencing panel can take a couple of weeks, depending on the laboratory and the methods used. Your team may wait for these results before finalising treatment, because a positive biomarker can change the first treatment from chemotherapy to a targeted tablet or immunotherapy. The wait can feel hard, but it helps make sure the treatment you start is the right one for your cancer. At CION, we keep you informed and order tests promptly so you are not left waiting longer than necessary.

KRAS is one of the more common gene mutations in lung cancer. For many years it was considered untreatable with targeted drugs, but that has changed: certain KRAS subtypes now have approved targeted medicines, and research continues to expand the options. Even where no targeted drug fits a particular KRAS change, knowing the result is useful — it helps your team plan the most suitable treatment and avoid approaches that are unlikely to work. KRAS testing is often part of a wider panel run by next-generation sequencing, so it is checked alongside other markers in one go.

Biomarker testing is most important in non-small cell lung cancer, particularly adenocarcinoma and especially in advanced disease, where a targetable change can directly change the first treatment. It is less central in small cell lung cancer, which is managed differently. Your oncologist chooses which markers to test based on your cancer type, its stage, and whether a result would genuinely alter your options — there is no value in ordering a test that cannot change the plan. This is part of CION's commitment to no unnecessary tests and transparent costs, so every test that is done has a clear purpose.

A negative result — meaning no targetable change was found — is still genuinely useful. It tells your team which treatments are unlikely to help and focuses the plan on the approaches most likely to work for you, such as chemotherapy, immunotherapy, radiation, or surgery depending on your stage. It also avoids the disappointment and delay of trying a targeted drug that would not match your cancer. Your tumour board reviews the full picture — your scans, biopsy, biomarker results and general health — to recommend the best path. Not finding a marker does not mean fewer options; it means a clearer, better-matched plan.