NSCLC Pathobiology and Biomarkers

NSCLC is the most common lung cancer in the US and is a heterogeneous disease consisting of 3 major subtypes1,2

NSCLC=non-small cell lung cancer; SCLC=small-cell lung cancer.

Colors indicate the estimated prevalence of NSCLC subtypes and are for illustrative purposes only.
The model does not represent individual patients.

NSCLC=non-small cell lung cancer; SCLC=small cell lung cancer.

Scroll down to learn more Down arrow
NSCLC Biomarkers

The molecular basis of lung cancer is complex and develops through a multistep process. Gene alterations and changes in protein expression contribute to the pathogenesis of NSCLC1

Currently, several testing options, such as NGS panels, are able to detect genetic alterations implicated in NSCLC. IHC testing represents a distinct methodology that captures changes in protein expression3

protein expression
genetic alterations
PD-L1 Protein Overexpression
~30%
c-Met Protein Overexpression*
~25%
Role in Oncogenesis4–6
Associated with immune evasion of cancer cells
Associated with cancer cell growth
Detection Method7,8
IHC
IHC
Approval Status3,9,10
FDA-approved CDx to identify appropriate patients for treatment
Emerging biomarker in research. Non-FDA approved CDx
PD-L1 Protein Overexpression
~30%
Role in Oncogenesis4–6
Associated with immune evasion of cancer cells
Detection Method7,8
IHC
Approval Status3,9,10
FDA-approved CDx to identify appropriate patients for treatment
c-Met Protein Overexpression*
~25%
Role in Oncogenesis4–6
Associated with cancer cell growth
Detection Method7,8
IHC
Approval Status3,9,10
Emerging biomarker in research.
Non-FDA approved CDx
This is not an exhaustive list of NSCLC biomarkers.

*EGFR-WT NSQ NSCLC. CDx=companion diagnostics; EGFR=epidermal growth factor receptor; FDA=Food and Drug Administration; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer; PD-L1=programmed death-ligand 1.

Oncogenic Mutations in NSCLC
Oncogenic mutations in NSCLC graphic
Role in Oncogenesis1,11
Genetic alterations include activation of growth-promoting proto-oncogenes (eg, KRAS, EGFR) and inactivation of tumor suppressor genes (eg, TP53)
Detection Method12,13
NGS, RT-PCR, FISH, Sanger sequencing
Approval Status3
Several FDA-approved tests available to identify patients with actionable mutations
Oncogenic Mutations in NSCLC
Oncogenic mutations in NSCLC graphic
Role in Oncogenesis1,11
Genetic alterations include activation of growth-promoting proto-oncogenes (eg, KRAS, EGFR) and inactivation of tumor suppressor genes (eg, TP53)
Detection Method12,13
NGS, RT-PCR, FISH, Sanger sequencing
Approval Status3
Several FDA-approved tests available to identify patients with actionable mutations
This is not an exhaustive list of NSCLC biomarkers.

ALK=anaplastic lymphoma kinase; BRAF=B-Raf; EGFR=epidermal growth factor receptor; ERBB2=erb-b2 receptor tyrosine kinase 2; ex14=exon 14; FDA=Food and Drug Administration; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry; KRAS=kirsten rat sarcoma viral oncogene homolog; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer; NTRK=neurotrophic tyrosine receptor kinase; PD-L1=programmed death-ligand 1; RET=rearranged during transfection; ROS=ROS proto-oncogene; RT-PCR=reverse transcription polymerase chain reaction; TP53=tumor protein 53.

References
  1. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398(10299):535-554. doi:10.1016/S0140-6736(21)00312-3
  2. Sainz de Aja J, Dost AFM, Kim CF. Alveolar progenitor cells and the origin of lung cancer. J Intern Med. 2021;289:629-635. doi:10.1111/joim.13201
  3. List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated May 1, 2024. Accessed June 4, 2024. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
  4. Pawelczyk K, Piotrowska A, Ciesielska U, et al. Role of PD-L1 expression in non-small cell lung cancer and their prognostic significance according to clinicopathological factors and diagnostic markers. Int J Mol Sci. 2019;20(4):824. doi:10.3390/ijms20040824
  5. Liang H, Wang M. MET oncogene in non-small cell lung cancer: mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510. doi:10.2147/OTT.S231257
  6. Fu F, Deng C, Sun W, et al. Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer. Respir Res. 2022;23(1):302. doi:10.1186/s12931-022-02201-8
  7. Scheel AH, Schäfer SC. Current PD-L1 immunohistochemistry for non-small cell lung cancer. J Thorac Dis. 2018;10(3):1217-1219. doi:10.21037/jtd.2018.02.38
  8. Park S, Choi YL, Sung CO, et al. High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol. 2012;27(2):197-207. doi:10.14670/HH-27.197
  9. Motwani M, Panchabhai S, Bar J, et al. P60.12 Prevalence of c-Met overexpression (c-Met+) and impact of prior lines of treatment on c-Met protein expression in NSCLC. J Thorac Oncol. 2021;16(10):S1169-S1170. doi:10.1016/j.jtho.2021.08.633
  10. Sun W, Song L, Ai T, et al. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer. J Biomed Res. 2013;27(3):220-230. doi:10.7555/JBR.27.20130004
  11. Cooper WA, Lam DC, O’Toole SA, Minna JD. Molecular biology of lung cancer. J Thorac Dis. 2013;5(suppl 5): S479-S490. doi:10.3978/j.issn.2072-1439.2013.08.03
  12. Michaels E, Bestvina CM. Meeting an un-MET need: targeting MET in non-small cell lung cancer. Front Oncol. 2022;12:1004198. doi:10.3389/fonc.2022.1004198
  13. Das R, Jakubowski MA, Spildener J, Cheng YW. Identification of novel MET Exon 14 skipping variants in non-small cell lung cancer patients: a prototype workflow involving in silico prediction and RT-PCR. Cancers (Basel). 2022;14(19):4814. doi:10.3390/cancers14194814
Developed and authored by AbbVie US Medical Affairs.
© 2024 AbbVie Inc. All rights reserved.
ABBV-US-01338-MC, v3.0
Approved: July 2024
Unless otherwise specified, all product names appearing in this internet site are trademarks owned by or licensed to AbbVie Inc., its subsidiaries or affiliates. No use of any AbbVie trademark, trade name, or trade dress in this site may be made without the prior written authorization of AbbVie Inc., except to identify the product or services of the company.
Accessibility Statement
Medical Information
Contact Us
Terms of Use
Privacy Notice
Cookies Settings
Your Privacy Choices
Privacy options
AbbVie logo

c-Met protein overexpression and MET amplification are emerging biomarkers and in clinical research as potential therapeutic targets. There are no FDA-approved tests for c-Met protein overexpression or MET amplification. Prognosis statements and prevalence estimates are based on multiple sources; survival and prevalence data can vary among studies and datasets because of detection methodology used, patient sample sizes and/or demographics/characteristics. Some patients may have more than one MET aberration and may have overlap with other NSCLC biomarkers.