Modern lung cancer treatment begins long before the first therapy is administered. For patients with advanced non-small cell lung cancer (NSCLC), one of the most important early steps is understanding the molecular and biological characteristics of the tumour. This process — known as molecular profiling or biomarker testing — has transformed the way lung cancer is treated and is now central to how oncologists make treatment decisions.
Dr Dionysis Papadatos-Pastos, a consultant medical oncologist specialising in lung cancer in London, explains what molecular profiling involves, which markers are tested, and why the results matter for treatment planning.
Topics Covered
Topics Covered
Topics Covered
Topics CoveredWhat Is Molecular Profiling?
Molecular profiling is the process of analysing a tumour at the genetic and molecular level to identify specific alterations that may be driving its growth. Rather than treating all lung cancers in the same way, molecular profiling allows oncologists to understand the biology of an individual patient’s cancer and select therapies that are matched to it.
In advanced NSCLC, this information is not optional — it is fundamental. The results of molecular testing directly determine which treatment is most appropriate from the outset, and can make the difference between a therapy that is highly effective and one that is unlikely to work.
Why Molecular Profiling Matters in Advanced NSCLC
Lung cancer is not a single disease. Even within non-small cell lung cancer, different tumours are driven by different molecular mechanisms. Two patients with the same stage of NSCLC may have entirely different molecular profiles and require entirely different treatments.
Without molecular profiling, treatment decisions are made with incomplete information. With it, oncologists can identify patients who are likely to respond well to a specific targeted therapy or immunotherapy regimen, and avoid treatments that are less likely to be effective for their particular tumour biology.
The importance of this approach is reflected in clinical guidelines across the UK and internationally, which recommend comprehensive molecular testing as a standard part of the assessment for all patients with advanced NSCLC.
What Is Tested in Molecular Profiling?
A comprehensive molecular profiling panel for advanced NSCLC typically includes assessment of the following:
EGFR (Epidermal Growth Factor Receptor) — Mutations in EGFR, particularly exon 19 deletions and the L858R mutation in exon 21, predict response to EGFR tyrosine kinase inhibitors. Less common subtypes, including exon 20 insertions, require different treatment approaches.
ALK (Anaplastic Lymphoma Kinase) — ALK gene fusions occur in a small but important subset of NSCLC and are highly sensitive to ALK inhibitors.
ROS1 — ROS1 gene rearrangements define a distinct molecular subtype that is responsive to ROS1-targeted therapies.
KRAS G12C — A specific KRAS mutation for which targeted inhibitors are now available in selected patients.
MET — MET exon 14 skipping mutations represent a targetable driver that can be treated with MET inhibitors.
RET — RET fusions are a less common but important molecular subtype for which targeted therapies exist.
BRAF V600E — This specific BRAF mutation can be treated with a combination of BRAF and MEK inhibitors.
NTRK — NTRK fusions are rare but respond well to TRK inhibitors across tumour types.
PD-L1 expression — PD-L1 is not a mutation but a protein whose expression level on tumour cells predicts the likelihood of response to immunotherapy.
TMB (Tumour Mutational Burden) — In some settings, TMB provides additional information about the likelihood of benefit from immunotherapy.
How Is Molecular Testing Performed?
Molecular testing is most commonly performed on tumour tissue obtained through biopsy. A pathologist analyses the tissue sample, and a molecular testing laboratory examines the genetic material within the tumour cells.
In situations where tissue is limited or difficult to obtain, liquid biopsy — analysis of circulating tumour DNA from a blood sample — can provide valuable molecular information. Liquid biopsy is increasingly used for initial testing and for monitoring treatment response or detecting resistance mutations over time.
Not all testing platforms are equivalent. Next-generation sequencing (NGS) panels are now considered the preferred approach because they can simultaneously test for multiple molecular alterations from a single tissue sample, reducing the risk of a clinically relevant marker being missed.
How Results Guide Treatment Decisions
The results of molecular profiling directly shape the treatment plan in several important ways.
When a targetable driver mutation is identified — such as an EGFR mutation, ALK rearrangement or ROS1 fusion — a matched targeted therapy is typically recommended as the preferred first-line treatment. These therapies are often more effective and better tolerated than chemotherapy for patients whose tumours carry these specific alterations.
When no targetable driver mutation is found, PD-L1 expression becomes a key consideration. High PD-L1 expression may support the use of immunotherapy alone or in combination with chemotherapy. Lower PD-L1 expression does not exclude immunotherapy but may influence which treatment combination is selected.
When both PD-L1 is low and no driver mutation is present, chemotherapy — often combined with immunotherapy — remains an important option, and clinical trial eligibility is always worth assessing.
Understanding that treatment decisions flow from molecular results is important for patients. It explains why treatment does not always begin immediately after diagnosis: waiting for complete molecular profiling results allows the oncology team to make a better-informed first treatment decision, which matters considerably in the long term.
The Role of the MDT in Interpreting Results
Molecular profiling results are most valuable when interpreted within the context of a specialist multidisciplinary team (MDT) that includes medical oncologists, pathologists, radiologists and other relevant specialists. In complex cases — including those with uncommon molecular alterations or overlapping results — specialist discussion ensures that the clinical implications of the testing are correctly applied to the treatment plan.
For patients whose tumours carry rare mutations or complex molecular profiles, referral to or consultation with a specialist precision oncology centre may be beneficial.
Molecular Profiling and Access to Clinical Trials
Molecular profiling also opens the door to clinical trial participation. Many trials in lung cancer are now molecularly stratified — meaning eligibility depends on the presence or absence of specific molecular alterations. Without comprehensive molecular testing, a patient may be unaware of trials for which they could be eligible and which might offer access to treatments not yet available in standard care.
Dr Papadatos-Pastos, as Lung Cancer Lead at the CRUK UCL Clinical Trials Centre, works closely with clinical research teams and is well placed to identify trial opportunities relevant to individual molecular profiles.
Private Specialist Care and Molecular Profiling
For patients in the private setting, a specialist consultation offers the opportunity to review existing molecular testing results in detail, discuss what the findings mean in practical terms, and ensure that no clinically relevant marker has been missed or underinterpreted.
Private specialist care also enables rapid access to comprehensive molecular profiling where this has not yet been arranged, and to expert guidance on the treatment implications of results — including emerging therapies and clinical trial options that may not be routinely discussed in a busy NHS outpatient setting.
Conclusion
Molecular profiling and biomarker testing are now fundamental to the management of advanced NSCLC. The results guide treatment selection from the outset, influence eligibility for targeted therapies and immunotherapy, and open access to clinical trials.
For patients who want to ensure that their molecular results have been fully interpreted and that all treatment options have been considered, a private specialist consultation with a thoracic oncology expert can provide both clarity and confidence in the treatment plan.
If you would like to discuss your molecular profiling results or explore the treatment options available for your lung cancer, Dr Papadatos-Pastos sees patients privately at several London clinics and is available for both in-person and virtual consultations.
Support and Follow-Up Care
Dr Papadatos-Pastos and his team provide ongoing support beyond medical treatment.
Patients receive clear communication, psychological care and access to nutrition, physiotherapy and symptom-management services.
Regular follow-up ensures early detection of recurrence and long-term wellbeing.
Book a Consultation
If you or someone close to you has been diagnosed with lung cancer, early consultation with a specialist can make a real difference. Appointments are available at several London clinics.
Faq
Answers to Common Questions
Common questions from patients and families about molecular profiling, biomarker testing and how results influence treatment decisions in advanced non-small cell lung cancer.
Molecular profiling is the analysis of a tumour’s genetic and biological characteristics to identify specific alterations that may be driving its growth. In advanced NSCLC, the results directly guide which treatment is most appropriate for each individual patient.
Because different tumours are driven by different molecular mechanisms, treatment decisions made without this information are less precise. Molecular testing allows oncologists to match therapy to the biology of each patient’s cancer, which can significantly improve outcomes.
A comprehensive panel for advanced NSCLC typically includes EGFR, ALK, ROS1, KRAS G12C, MET, RET, BRAF V600E, NTRK and PD-L1. Tumour mutational burden (TMB) may also be assessed in some settings.
Testing is usually performed on tumour tissue obtained through biopsy. Where tissue is limited, liquid biopsy — analysis of circulating tumour DNA from a blood sample — can provide useful molecular information. Next-generation sequencing (NGS) panels are the preferred approach as they can assess multiple markers simultaneously.
If a targetable driver mutation is identified — such as an EGFR mutation or ALK rearrangement — a matched targeted therapy is typically recommended as the preferred first-line treatment. These therapies are often more effective and better tolerated than chemotherapy in this setting.
If no targetable driver mutation is present, PD-L1 expression guides decisions around immunotherapy. Chemotherapy combined with immunotherapy remains an important option, and clinical trial eligibility is always worth considering.
Waiting for complete molecular profiling results allows the oncology team to make a better-informed initial treatment decision. Starting treatment before these results are available may mean selecting a less appropriate first therapy, which can affect outcomes.
Yes. Many lung cancer trials are stratified by molecular profile, meaning eligibility depends on the presence or absence of specific alterations. Comprehensive molecular testing ensures that patients are aware of all trials for which they may qualify.
Yes, particularly when results are complex, when rare mutations are present, or when the treatment implications are unclear. A private specialist consultation can provide an independent expert review of molecular testing results and their treatment implications.
