What causes erlotinib resistance?

The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene.

What are the most typical mechanisms of acquired resistance identified in lung cancer patients treated with EGFR TKIs?

Depending on the mutation present in EGFR, tumors exhibit differential TKI sensitivities. While the most common EGFR-activating mutations, L858R and exon 19 deletion, typically confer sensitivity to EGFR TKIs, other primary EGFR mutations can confer resistance.

How does EGFR TKI work?

The working mechanism of first-generation EGFR-TKIs is to block the activation of downstream signaling induced by EGFR through binding to the ATP-binding sites.

How does T790M resistance occur?

The most common resistance mechanism results from the development of the so-called ‘gatekeeper’ T790M mutation in EGFR exon 20, which sterically hinders the binding of first- and second-generation TKIs to the ATP-binding site of EGFR.

Is Tarceva a TKI?

Erlotinib is a tyrosine kinase inhibitor (TKI) which is a type of cancer growth blocker. It blocks proteins on cancer cells that encourage the cancer to grow. These proteins are called epidermal growth factor receptors (EGFR). If you have a cancer that has these receptors you are EGFR positive.

What are EGFR activating mutations?

Kinase domain mutations in EGFR are referred to as ‘activating mutations’ because they lead to a ligand-independent activation of TK activity. In some tumors, partially activated mutant EGFRs can be rendered fully ligand independent and, therefore, constitutively active by a second mutation.

What are EGFR mutations?

An EGFR mutation refers to a mutation (damage) to the portion of the DNA in a lung cancer cell which carries the “recipe” for making EGFR (epidermal growth factor receptor) proteins.

What is an EGFR inhibitor?

ABSTRACT: Epidermal growth factor receptor (EGFR) inhibitors are a class of drugs used to treat several common malignancies, including breast, colon, lung, and pancreatic cancer. Cutaneous adverse reactions have been reported to occur in approximately 90% of patients treated with an EGFR inhibitor.

What is C797S?

C797S mutation mediates resistance to HM61713 HM61713 (BI 1482694) is another third-generation EGFR inhibitor and covalently binds to a cysteine residue near the kinase domain of mutant EGFR [18, 19]. In a phase I/II study, HM61713 was shown to be active for patients with T790M-positive NSCLC [5].

How long can you stay on Tarceva?

In the SELECT clinical trial 100 patients with stage IA to IIIA NSCLC were treated with oral Tarceva for up to 2 years following surgical removal of their cancer.

Is erlotinib an immunotherapy?

Drugs that target epidermal growth factor receptor (EGFR) mutations (eg, gefitinib, erlotinib, icotinib, and osimertinib) are among the most commonly used targeted therapies.