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EGFR-TKIs inibitors

Saturday 25 November 2006

EGFR antagonists; EGFR inhibitors

Resistance to EGFR inhibitors

Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges.

All drug-resistant tumors retain their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR-T790M mutation or MET gene amplification.

Some resistant cancers show unexpected genetic changes including EGFR amplification and mutations in the PIK3CA gene, whereas others undergo a pronounced epithelial-to-mesenchymal transition. (Sequist et al., 2012)

Surprisingly, some resistant tumors (14%) can transform from NSCLC into small cell lung cancer (SCLC) and are sensitive to standard SCLC treatments. (Sequist et al., 2012)

In some patients, serial biopsies revealed that genetic mechanisms of resistance were lost in the absence of the continued selective pressure of EGFR inhibitor treatment, and such cancers are sensitive to a second round of treatment with EGFR inhibitors. (Sequist et al., 2012)

See also


Open references

- Novel small molecule EGFR inhibitors as candidate drugs in non-small cell lung cancer. Berardi R, Santoni M, Morgese F, Ballatore Z, Savini A, Onofri A, Mazzanti P, Pistelli M, Pierantoni C, De Lisa M, Caramanti M, Pagliaretta S, Pellei C, Cascinu S. Onco Targets Ther. 2013 May 21;6:563-76. doi : 10.2147/OTT.S28155 PMID: 23723712 [Free]


- Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors,

- Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008 Mar 13;358(11):1160-74. PMID: 18337605

- Nyati MK, Morgan MA, Feng FY, Lawrence TS. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer. 2006 Nov;6(11):876-85. PMID: 17036041

- Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006 Oct;6(10):803-12. PMID: 16990857

- Herbst RS, Fukuoka M, Baselga J. Gefitinib—a novel targeted approach to treating cancer. Nat Rev Cancer. 2004 Dec;4(12):956-65. PMID: 15573117