A malignant transformation within a lung cell is thought to follow activation of proto-oncogens and/ or impaired activity of tumor-suppressor genes. Proto-oncogens regulate the normal growth and devolopment within a particular cell. The expression of proto-oncogens is normally under tight control. When malignant transformation occurs, this tight control is lost and proto-oncogens are activated through several pathways. ErbB-1 and myc are proto-oncogens. P53 on chromosome 17 is a tumor-suppressor gene.
Malignant transformation occurs in one clone of cells. These cells differentiate further along one or more cell lines, leading to the various histological types (sometimes mixed types) of lung cancer.