What is "EGFR-positive NSCLC"?

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EGFR stands for Epidermal Growth Factor Receptor. This is a protein on cells that is a receptor for Epidermal Growth Factor EGF. EGF is one of many growth factors that are present in the blood. Activation/signalling of EGFR by EGF results in biochemical processes that support cell growth, proliferation and migration [1].

EGFR Signalling

NSCLC stands for “Non Small Cell Lung Cancer” or “Non Small Cell Lung Carcinoma”. About 80%-85% of lung cancers are NSCLC [2].

EGFR-positive NSCLC is a form of NSCLC that is driven by a mutation (or mutations) in the gene for EGFR. This mutation causes the EGFR protein to be mis-shapen in some way. This may result in a protein that can be activated even when it is not bound to a ligand like EGF, or simply a protein that has an increased response to EGF (activating mutations). Consequently, tumour cells receive increased signals to proliferate and survive. Perhaps 10% of Caucasians and 50% of Asians with NSCLC have this class of mutation [3].

The EGFR gene (as opposed to the protein it encodes) is composed of 28 exons (DNA sequences within a gene). The resulting protein has 1210 amino acids. Mutations in EGFR typically occur in exons 18, 19, 20 or 21. Such mutations might be point mutations of single amino acids, deletions of one or more amino acids, or insertions/duplications of amino acids [4]. For example:


Example deletion: KIPVAIK…………..TSPKANKEILD ( “delE746_A750” )

Exon 20 wild type: EAYVMASVDNPHVCR

Example insertion: EAYVMASVDNPGNPHVCR ( “D770_N771insNPG” )

The amino-acid representation for the EGFR exons has been used above, rather than the base-pair representation. Triplets of 4 different base pairs (A, T, G, C) combine to form one of 20 different amino acids (A, R, N, D, C, E, Q, G, H, I, L, K, M, F, P, S, T, W, Y, V) so the base-pair representation of EGFR would be three times as long as the amino-acid representation.

The following therapies are applicable to EGFR-positive NSCLC:

  • Targeted genetic therapies. These are typically small-molecule drugs, usually taken in tablet form, that attempt to inhibit the function of the EGFR mutation that drives the cancer. The main example is TKIs.

  • Chemotherapy.

  • Radiotherapy.

  • Immunotherapies.

  • Exercise

  • Diet


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