2012/08/31 12:32

Case study 7

Pemetrexed is a drug recommended for the treatment of non–small-cell lung cancer with a nonsquamous histology. Which protein is a potential predictive marker for response to pemetrexed-based chemotherapy?

  •  Alkaline phosphatase

  •  Thymidylate synthase

  •  EGFR (epidermal growth factor receptor)-mutated protein

  •  HER2 (human epidermal growth factor receptor 2)

  •  ERCC-1 (excision repair cross-complementation group 1)

Explanation
Pemetrexed inhibits several folate-dependent enzymes, including thymidylate synthase (TS). This enzyme is highly expressed in squamous cell carcinoma, whereas there is low expression in adenocarcinoma, which suggests an inverse correlation between TS expression and tumor response to pemetrexed because the drug is not effective in treating squamous cell carcinoma. Pemetrexed is recommended for use in pulmonary carcinoma of nonsquamous histology. Even among nonsquamous carcinoma, the response to pemetrexed is heterogeneous. Recently, immunohistochemical stains to measure the expression of TS in tumor cells have been used experimentally. These studies have indicated that determination of the levels of TS expression correlates with response to pemetrexed treatment, confirming that overexpression of TS is associated with resistance to treatment. Therefore, immunohistology to evaluate the level of expression of TS has the potential to be a predictive marker of response and could be used by pathologists in the workup of pulmonary adenocarcinoma cases.1,2 Validation of this marker for clinical use is pending.
References
    1.    Andrews J, Yeh P, Pao W, Horn L. Molecular predictors of response to chemotherapy in non-small cell lung cancer. Cancer J. 2011;17:104-113.
    2.    Takezawa K, Okamoto I, Okamoto W, et al. Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer. Br J Cancer. 2011;104:1594-1601.


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