Non-small-cell lung cancer: molecular targeted therapy and personalized medicine – drug resistance, mechanisms, and strategies

Figures & data

Table 1 Summary of the current therapies, their targets, and their function

Drug	Class	Target	Pathway
Gefitinib, erlotinib	Tyrosine kinase inhibitor	EGFR	PI3K/Akt – survival
			MAPK – proliferation
Cetuximab	Monoclonal antibody	EGFR	PI3K – survival
			MAPK – proliferation
Crizotinib	Tyrosine kinase inhibitor	ALK	MAPK – proliferation
Bevacizumab	Monoclonal antibody	VEGF	Angiogenesis
Sunitinib, sorafenib	Tyrosine kinase inhibitor	VEGF	Angiogenesis
Vorinostat	Small molecule inhibitor	Histone deacetylase	Epigenetic silencing
Cixutumumab	Tyrosine kinase inhibitor	IGF-1R	PI3K/Akt, DNA damage
Figitumumab	Monoclonal antibody	IGF-1R	PI3K/Akt, DNA damage
Celecoxib	Small molecule inhibitor	COX-2	EGFR signaling – PI3K/Akt – MAPK

Abbreviations: EGFR, epidermal growth factor receptor; VEGF, vascular endothelial growth factor; IGF, insulin-like growth factor; PI3K, phosphatidylinositide 3-kinase; MAPK, mitogen-activated protein kinase; COX-2, Cyclooxygenase-2.

Figure 1 A hypothetical line of treatment based on the availability of a range of targeted therapies.

Notes: An initial tumor is treated with its appropriate therapy. Upon resistance via mutations or clonal selection, the cancer can be sensitized with a different drug. This process of personalized medicine might not cure the disease, but rather keeps the disease under constant submission.
Abbreviations: ALK, anaplastic lymphoma kinase; ELM4, echinoderm microtubule-associated protein-like 4; EGFR, epidermal growth factor receptor.