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Lung Cancer Biomarkers - An Overview

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Despite advancements, lung cancer remains the leading cause of death worldwide and has a terrible prognosis; lung cancer biomarkers help with that.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At March 27, 2024
Reviewed AtMarch 27, 2024

Introduction

To diagnose cancer, clinicians use biomarker testing, also known as molecular testing or tumor marker testing, to study tumor tissue from a biopsy or blood sample. Cancer patients have elevated biomarkers in their blood, urine, or tissues. DNA mutations, alterations, and patterns in tumors are the various biomarkers.

What Is a Lung Cancer Biomarker?

Lung cancer biomarkers encompass proteins, hormones, or DNA fragments that are either secreted by cancer cells or released by the body as a reaction to the presence of cancer. Biomarker testing can be conducted by a medical practitioner or other healthcare expert to assess the presence of certain biomarkers in an individual's body.

Historically, a uniform treatment approach was employed for all individuals diagnosed with lung cancer. Currently, therapeutic interventions are specifically tailored to individuals based on their biomarkers.

Biomarkers play a crucial role in prognosticating optimal therapy modalities/care for cancer patients; they can serve as indicators of treatment efficacy. Medical professionals employ it to facilitate the diagnosis of cancer and determine its potential rate of progression. Although biomarkers are present for small-cell lung cancer, their predominant application lies in the diagnosis and management of non-small cell lung cancer (NSCLC).

Why Can Biomarker Testing Benefit Lung Cancer Patients?

Targeted therapy can address many of these mutations. These targeted medicines have been shown to treat lung tumors with certain mutations in clinical trials. Targeted therapy targets cancer-promoting genes, proteins, and tissue environments. These medicines can slow, stop, or kill cancer. Knowing which indicators the lung cancer has may allow one to utilize targeted therapy to inhibit mutations that are fueling its development and survival. For advanced lung cancer and possibly other stages of lung cancer, biomarker testing is essential to therapy planning. Targeted therapy may have fewer negative effects since it protects healthy cells.

When Does Biomarker Testing Accompany Lung Cancer Treatment?

People with stage IV or advanced non-squamous NSCLC benefit the most from biomarker testing. A broad testing panel, like next-generation sequencing (NGS), can be used for biomarker testing because there are so many different types of biomarkers. Biomarker testing may be given to people with advanced squamous cancer who have little to no smoking history, have tumors with a mix of squamous and non-squamous components, or both.

In addition to advanced NSCLC, biomarker testing may be carried out on some patients with early stages of the disease and, less frequently, on some patients with small cell lung cancer (SCLC). As EGFR and ALK gene mutations are frequent in early-stage disease and can be treated with targeted therapy, one may specifically advise restricted biomarker testing to screen for these changes. Many oncologists may also consider biomarker testing when making decisions about stage I to stage III NSCLC. The use of biomarker testing as a standard of care for lung cancer that is not stage IV is still unclear, though.

What Are the Classifications of Biomarkers?

Lung cancer biomarkers are mutations caused by gene alterations or rearrangements that encourage cancer cell development.

  • Immune Response Biomarkers: These biomarkers determine how effectively immunotherapy will work for one’s malignancy. NSCLC gene mutation biomarkers include:
  • Tumor Protein p53 (TP53): The most prevalent mutation in NSCLC is TP53. It is seen in around 50 percent of persons with NSCLC.

  • KRAS: The second most prevalent mutation in NSCLC is KRAS. The KRAS mutation is found in approximately 30 percent of persons with NSCLC. The serine/threonine kinase 11 (STK11) mutation is frequently found alongside it.

  • EGFR: The epidermal growth factor receptor (EGFR) mutation causes the creation of the EGFR protein, which causes cancer cells to grow excessively. There are several EGFR mutations, the most frequent being EGFR exon 19 deletion and EGFR exon 21 L858R point mutations.

  • Anaplastic Lymphoma Kinase: The ALK gene can be relocated or fused to another gene, such as the echinoderm microtubule-associated protein-like 4 (EML4) gene. ALK-positive lung cancer affects those around with NSCLC.

  • MET Gene and MET Exon 14(METex14): The MET gene codes for the MET protein, which transmits growth signals to the cancer. Exon 14 skipping is a defect that hinders the degradation of a certain type of MET protein, which results in extra protein in the body.

  • PIK3CA: The PIK3CA mutation affects the p110 alpha protein. This protein is required for lung cancer cell proliferation and survival.

  • BRAF: This mutation causes the creation of an aberrant protein, which causes cancer cells to grow excessively. BRAF mutations are found in persons with NSCLC.

  • Human Epidermal Growth Factor Receptor 2 (HER2): The HER2 gene mutation delivers signals that promote tumor growth. Breast and ovarian cancers are also associated with HER2 gene alterations. HER2 gene mutations are found in one to four percent of persons with NSCLC.

  • ROS1: This gene may be misplaced or fused to a portion of another gene. ROS1 is mutated in one to two percent of NSCLC patients.

  • RET: The RET gene may be positioned incorrectly or joined to another gene. This mutation is found in one to two percent of persons with NSCLC.

  • NTRK (Neurotrophic Tyrosine Receptor Kinase): The NTRK gene can combine with another gene, resulting in uncontrolled cell proliferation. This gene alteration affects approximately one percent of persons with NSCLC.

Non-small cell lung cancer (NSCLC) is associated with many biomarkers that are indicative of the immune response. Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are membrane-bound proteins expressed on T cells, a subset of healthy white blood cells. Furthermore, these receptors are found in higher concentrations on certain cancer cells. They function as an inhibitory mechanism to impede the immune system's assault on the cancerous cells. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein that plays a crucial role in regulating the immune response. Additionally, this protein is found on the surface of T cells. It hinders the immune system's ability to respond to malignancy.

What Are the Various Applications of Biomarker Testing?

Biomarker testing provides healthcare professionals with additional insights into the characteristics of a tumor. It is advisable for all individuals who have been diagnosed with non-small cell lung cancer (NSCLC) to undergo these tests. The specimen is sent to a laboratory or testing facility to examine DNA alterations and quantify certain protein levels. Several methods exist for the identification of biomarkers associated with lung cancer.

  • Next-generation sequencing (NGS) involves using a machine to analyze a tissue or blood sample, enabling the simultaneous identification of several biomarkers in a comprehensive manner.

  • Fluorescence in situ hybridization (FISH) is a molecular cytogenetic technique that employs a specialized fluorescent dye to detect the presence of cancer genes.

  • Immunohistochemistry (IHC) is a widely employed staining technique in biomedical research and clinical diagnostics. It involves the utilization of specific antibodies, which are proteins capable of binding to target biomarkers, to precisely identify and localize these biomarkers inside a given tissue sample.

Conclusion

Though progress has been made in recent years, the overall prognosis for lung cancer patients remains dismal, with lung cancer having a mortality rate that exceeds that of breast, colon, and prostate malignancies combined. Age, stage, and performance status will continue to play an important role in managing patients with this disease. Nevertheless, lung cancer is a heterogeneous disease, necessitating the development of more sophisticated methods for risk-stratifying patients and customizing treatments. Biomarkers have the potential to facilitate earlier disease detection, prognostication, and treatment decision-making. Although it is unlikely that a single marker will meet all these criteria, a better understanding of the multiple pathways involved in lung carcinogenesis may one day lead to improved outcomes.

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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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