MET DYSREGULATION IN NSCLC

 

MET normally plays an important role in cell signaling, proliferation, and survival1,2

 

MET pathway diagram
  • MET (mesenchymal-epithelial transition) factor is a receptor tyrosine kinase coded by the MET gene, and is expressed on the surfaces of various epithelial cells3

 

  • When HGF binds to the MET receptor, it activates the downstream pathway and triggers cell growth, proliferation, and survival4

 

Dysregulation of MET and HGF signaling leads to malignant cellular transformation, proliferation, survival, angiogenesis, invasion, and metastasis3

 

MET dysregulation can occur through a variety of mechanisms

MET receptor
overexpression

Occurs when there are too many copies of the MET receptor5

The role of MET receptor overexpression is unclear2

MET amplification

An increase in the number of copies of the MET gene6

MET amplification can occur as an oncogenic event or a mechanism of resistance2

MET alterations

METex14

Most commonly caused by splice site alterations2

METex14 is an oncogenic alteration in NSCLC2

MET rearrangement/fusion

A chromosomal rearrangement leading to gene fusion, resulting in a chimeric MET protein7

MET rearrangements/fusions are rare mechanisms, and their role as oncogenic alterations is unclear2

MET receptor overexpression

Occurs when there are too many copies of the MET receptor5

The role of MET receptor overexpression is unclear2

MET

amplification

An increase in the number of copies of the MET gene6

MET amplification can occur as an oncogenic event or a mechanism of resistance2

MET
alterations

METex14

Most commonly caused by splice site alterations2

METex14 is an oncogenic alteration in NSCLC2

MET rearrangement/fusion

A chromosomal rearrangement leading to gene fusion, resulting in a chimeric MET protein7

MET rearrangements / fusions are rare mechanisms and their role as oncogenic alterations is unclear2

 

 

METex14 subtype >

AKT, protein kinase B; HGF, hepatocyte growth factor; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; mTOR, mechanistic target of rapamycin; NSCLC, non-small cell lung cancer; PI3K, phosphoinositide 3-kinase; RAF, rapidly accelerated fibrosarcoma; STAT 3/5, signal transducer and activator of transcription 3/5.

 

 

References

1. Feng Y, Thiagarajan PS, Ma PC. J Thorac Oncol. 2012;7:459-467.
2. Drilon A, Cappuzzo F, Ou SI, Camidge DR. J Thorac Oncol. 2016;12(1):15-26.
3. Zhang Y, Xia M, Jin K, et al. Mol Cancer. 2018;1-14.
4. Mo HN, Liu P. Chron Dis Transl Med. 2017;3:148-153.
5. NCI Dictionary of Cancer Terms. Overexpress. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/overexpress. Accessed September 17, 2019.
6. NCI Dictionary of Cancer Terms. Gene amplification. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gene-amplification. Accessed September 17, 2019.
7. Duplaquet L, Kherrouche Z, Baldacci S, et al. Oncogene. 2018;37:3200-3215.

 

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