Your Genes, Your Treatment: Biomarker Testing and Lung Cancer

Biomarker testing for nearly a dozen oncogenes is helping transform lung cancer care from a one one-size-fits-all approach into an individually tailored treatment approach.

“Biomarker testing can be really useful,” Dr. Anne Chiang said in an interview following her presentation at the CURE Educated Patient® Lung Cancer Summit, held in tandem with the 2025 PER® New York Lung Cancer Symposium. “We now test for 11 oncogene biomarkers at time of diagnosis, for use of their targeted therapies. You can use biomarkers throughout the course of disease. This is a really exciting area of research now.”

Chiang is an associate professor of the Division of Thoracic Medical Oncology at Yale University School of Medicine, and associate cancer care director of clinical initiatives at Yale Cancer Center in New Haven, CT. In her presentation, she discussed how the information contained in a lung tumor's DNA can shape an individual patient’s treatment plan. 

What Are Biomarkers, and How Are They Useful?

Biomarkers are essentially a characteristic tumor marker found on tumor tissue cells or circulating tumor cells in the blood. Testing for biomarkers (which are defined as tumor genetic testing, genetic profiling, subtyping, and molecular profiling, among other terms) can be useful for diagnostic (to characterize a cancer type), prognostic (to indicate the aggressiveness of a patient’s cancer), and predictive purposes (to predict the benefit to a specific treatment).

Molecular biomarkers can be further broken down into the following analyses:

• Genomic profiling: refers to the study of genes or DNA
• Transcriptomics: the study of RNA transcripts
• Proteomics: the study of proteins

Physicians can examine biomarkers both in tissue, known as a tissue biopsy, or in the blood, known as a liquid biopsy, as well as diagnostic imaging. Tissue biomarkers remain the gold standard for biomarker detection, Chiang explained.

“If you don't have very high tumor burden, or have very early-stage disease, you may not have any circulating tumor molecules in the blood, so [a liquid biopsy] might be negative, even though you have cancer cells elsewhere,” Chiang explained. “The other thing that we like about liquid biopsies, for example, is that it can also reflect biomarkers from different parts of your different sites of your disease.”

Compared with prior practice — for context, in 2012, EGFR was the only oncogene being tested for — it is now standard to test for 11 oncogene therapies at the time of an non–small cell lung cancer (NSCLC) diagnosis. When a patient’s disease is matched up with a biomarker that has appropriate targeted therapies, it allows for the patient to then be eligible for that personalized treatment.

“In 2025, the guidelines show that we have 11 different oncogenes that should be tested at the time of diagnosis for advanced NSCLC, and we have almost 40 different targeted therapies to treat, instead of just two,” Chiang said.

Genomic alterations with available targeted agents are as follows:

1. EGFR mutations: Tagrisso (osimertinib), Tarceva (erlotinib), Gilotrif (afatinib), (dacomitinib), Rybrevant (amivantamab) plus Lazcluze (lazertinib) or chemotherapy
2. ALK rearrangements: Alecensa (alectinib), Alunbrig (brigatinib) Zykadia (ceritinib), Xalkori (crizotinib), Lorbrena (lorlatinib), Ensacove (ensartinib)
3. ROS1 rearrangements: Xalkori, Zykadia, Rozlytrek (entrectinib), repotrectinib (Augtyro)
4. BRAF V600E mutations: Tafinlar (dabrafenib) plus Mekinist (trametinib), Braftovi (encorafenib) plus Mektovi (binimetinib), Zelboraf (vemurafenib)
5. HER2 mutations: Gilotrif, Kadycla (ado-trastuzuman emansine), Enhertu (fam-trastuzumab deruxtecan-nxki)
6. MET amplification/mutation: Xalkori, Trabecta (capmatinib), Tepmetko (tepotinib)
7. RET rearrangements: Cabometyx (cabozantinib), Caprelsa (vandetanib), selpercatinib (Retevmo), Gavreto (pralsetinib)
8. NTRK rearrangements: Rozlytrek, Vitrakvi (larotrectinib), Augtyro
9. EGFR exon 20 insertion mutations: Rybrevant plus or minus chemotherapy, Zegfrovy (sunvozertinib)
10. KRAS G12C: Lumakras (sotorasib), Krazati (adagrasib)
11. NRG1: Bizengri (zenocutuzumab)

Biomarkers can be tested for and serve informational purposes throughout a patient’s cancer journey. For example, in patients with advanced disease, biomarker identification is used to guide treatment choices by your physician to reduce your disease burden. Circulating tumor DNA (ctDNA) is utilized to track how a cancer is responded to the targeted treatment.

“At the time of progression, if your disease develops resistance, that's another time that you can use ctDNA to say, ‘Okay, are there new mutations? Is there something else that's a marker of resistance that I can actually target?’ That's how Tagrisso was developed — by doing biopsies at the time of resistance.”

In more recent years, ctDNA is also being analyzed in patients with earlier-stage disease to determine the presence of molecular residual disease following surgery and/or chemoradiation.

How to Understand the Nuances of Biomarkers in Lung Cancer

No two biomarkers are alike; for example, if a patient with NSCLC harbors high PD-L1 expression, they are generally more likely to respond to PD-1/PD-L1 inhibitors, such as Keytruda (pembrolizumab) or Opdivo (nivolumab). While patients with low or no PD-L1 expression may still respond to this class of immunotherapies, it is recommended for a combination of a PD-1/PD-L1 inhibitor and chemotherapy be used in this patient population.

In patients with advanced small cell lung cancer (SCLC), PD-L1 expression is not commonly seen in tumor cells and does not predict the benefit of checkpoint inhibitors. In the first-line treatment setting, immunotherapy is always given in combination with chemotherapy for these patients.

“We’re learning a lot more about this biomarker, and that will come across in the coming years,” Chiang said.

Along the unique lines, Chiang shared how antibody-drug conjugates have become an exciting biomarker-targeted approach in both NSCLC and SCLC treatment.

“I think of this as sort of like a targeted missile that will take your chemo directly to the cancer cell when it gets there,” Chiang said. “The antibodies recognize the protein. They're then internalized into the cell, into lysozymes, the chemotherapy linker is dissolved, and then that frees the chemotherapy directly in the cancer cell.”

Next Steps in Lung Cancer Biomarker Testing

Chiang shared how liquid biopsies from other types of body fluids are being evaluated for future biomarkers, including pleural effusion, blood, breastmilk, urine, salvia, and spinal fluid. Additionally extracellular vesicles, which are membrane-bound sacs that cells release into the extracellular space, are being studied as future biomarkers; they contain proteins, RNAs, and lipids. Though they are stable, extracellular vesicles are challenging to isolate.

“We're really learning more and more about cells diving deeper, and I think we're going to be able to provide more insights for our patients,” Chiang concluded.

Reference

1. "Biomarker testing," by Dr. Anne Chiang. CURE Educated Patient® Lung Cancer Summit; Nov. 15, 2025; New York, New York.

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