What is Erlotinib (Tarceva)?

Tarceva - Erlotinib

Mechanism of action of Erlotinib (Tarceva)

Erlotinib (Tarceva, Genentech), is a targeted cancer treatment approved for treating chemotherapy-resistant advanced non-small cell lung cancer (NSCLC). NSCLC is the most frequent cause of cancer death in the world. New treatments targeting the epidermal growth factor receptor (EGFR) is the focus of advancing NSCLC research and treatment. Erlotinib, an anti-EGFR molecule targeted agent, was approved by FDA in November 2004 and by European Medicinal Evaluation Agency (EMEA) in 2005.

Mechanism of Action of Erlotinib

Erlotinib is an EGFR inhibitor (tyrosine kinase inhibitor). Cancerous cells proliferate and grow when EGFR activates tyrosine kinase enzyme. Erlotinib inhibits this activation action of the growth factor receptors thereby prompting apoptosis or stagnation of cancer cell growth. The drug has also shown increased inhibitory activity on EGFR tyrosine kinases which are occasionally mutated.

  • When there is imbalance between cell division and apoptosis, over-proliferation of cells occur leading to cancer.
  • EGFR or HER family membrane receptors play central role in cell division regulation and cell death.
  • Of the 4 HER family receptors, Erlotinib reversibly binds with HER1.
  • Now, HER 1 has three parts:
    • Intracellular tyrosine kinase domain
    • Extracellular ligand binding domain
    • Transmembrane domain
  • Normally in a cell, when ligand binds with extracellular domain, HER1 is activated and forms a dimer with any of the HER family. This leads to transphosphorylation (ATP –phosphorylation) of intracellular tyrosine kinase domain.
  • There follows a cascade of multiple pathways leading to cell growth and proliferation.
  • HER1 dysregualtion can cause:
    • Overexpression of HER1
    • Increased signaling activity
    • EGFR mutations causing tumorigenicity
  • Erlotinib competes for the ATP site of HER1.
  • It blocks EGFR mediated downstream signaling activity.
  • Prevents overproliferation and increases apoptosis of cancer cells.
  • May restore normal function of cell.

In the wake of standard treatments like radiotherapy, chemotherapy, and surgery having plateaued out, new alternative to conventional treatments like Erlotinib has to be researched for improved lung cancer prognosis.

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