Manipulating the tumour-suppressor protein Rb in lung cancer reveals possible drug targets

Abstract

Tumours often become resistant to treatment, but how this occurs is poorly understood. An analysis of how the protein Rb affects tumour growth and the response to therapy might cast light on the problem.

Keywords: Cancer; Medical research.

Figure 1|. The Rb protein in cancer cells.

a, Rb is a type of protein known as a tumour suppressor, which can help to block cancer development. A common feature of lung cancer is Rb inactivation by the addition of phosphate groups (P) to the protein. This frequently occurs through a pathway that requires various enzymes: MAPK; Cdk4 and Cdk6; or Cdk2. b, Drugs that block the action of MAPK or Cdk4 and Cdk6 are in use in the clinic or under development for lung cancer treatment. Walter et al. studied a mouse model of lung cancer, and report that Cdk2 has a major role in inactivating Rb. Therefore, the development of drugs that target this protein might have promise in treating lung cancer, c, Rb expression is often lost in lung cancer cells (yellow). The authors studied the effect of Rb loss in mouse models of the cancer. The absence of Rb resulted in loss of cellular differentiation and an increase in the spread of cancer cells to other sites in the body through a process called metastasis. Proteins implicated in such changes, such as SOX2 and HMGA2, might offer targets for drug development.