A prognostic and predictive biomarker for nonsmall cell lung cancer

The era of one-size-fits-all medicine will eventually be history; after all it is no news that drugs and treatments do not work the same for everyone. For patients with nonsmall cell lung cancer (NSCLC), a lung cancer that kills approximately 1 million people annually, the treatment currently available is basically the same for all patients, despite the fact that some patients may respond to treatment while others may not. New biological markers and prognostic tools are urgently needed to help doctors decide on the best course of action for each NSCLC patient. It now appears that this reality is not years away, at least for NSCLC treatment.

Currently, NSCL prognosis is made based on patient's general performance and tumor staging. Still, doctors do not know which patients with NSCLC may survive for only 10 months and which for 5 years. Now, a study published ahead of print in the journal Cancer (“CFL1 expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer”, DOI 10.1002/cncr.25125) presents strong evidence that a protein called cofilin (CFL1) may help doctors in determining patient prognosis and in identifying those in need of a more aggressive treatment. The study also indicates that based on this protein, doctors may decide which drugs to use, and which to avoid, when treating NSCL patients. The possibility of doctors knowing before prescription which drugs are likely to work best for each patient represents a great advance in cancer treatment.

The group led by Dr. Fábio Klamt, a researcher at the Department of Biochemistry at the Federal University of Rio Grande do Sul, Brazil found that cofilin levels can be used to indicate which patients in the early stages of the disease have a good prognosis and which do not. When studying a large collection of NSCL cancer samples, the researchers found that the biopsies in which high levels of cofilin were found were from patients who had survived for shorter periods than those from patients with lower expression of the protein.

Besides the correlation found between cofilin and patient survival, the group also investigated whether cofilin levels could provide any clues on tumor aggressiveness. According to Dr. Klamt, “cofilin is a protein associated with cell mobility. We know that poor prognosis correlates with the ability of cells to move to generate metastasis. Thus, it seemed only reasonable that cells with lower levels of this protein would be less aggressive while higher levels would provide a more aggressive behavior.” Indeed, the group tested six human cell lines of 3 major types of NSCLC and found that the types with higher levels of cofilin presented a greater potential to invade other sites in the body, which indicates a more aggressive behavior. “For patients,” explains Dr. Klamt, “this finding indicates that lower levels of cofilin translate into lower chances to develop metastasis, which ultimately leads to a better prognosis.”

The group also found that high levels of cofilin correlate with resistance to certain anticancer drugs, especially cisplatin and carboplatin, which have long been used for treating NSCLC. Cisplatin-based chemotherapy is the standard first-line treatment for patients at an early stage and with good performance. Nevertheless, only some will respond to this treatment. Now cofilin levels may be used to distinguish between responders and non-responders. This new finding may have great impact on survival rates, as potential non-responders may benefit from different treatment options that would not be available otherwise.

The study was funded by the Brazilian Science and Technology Ministry/National Counsel of Technological and Scientific Development (MCT/CNPq), the MCT/CNPq National Institutes for Translational Medicine (INCT-TM), and the National Cancer Institute, National Institutes of Health (USA).

A patent concerning CFL1 expression levels as a prognostic biomarker for NSCLC has been recently filed with the Brazilian Patent Office (Instituto Nacional da Propriedade Industrial – INPI) under the number # PI0802917-2

Other researchers working on the study include Mauro Antonio Alves Castro, Felipe Dal-Pizzol, Stephanie Zdanov, Marcio Soares, Carolina Beatriz Müller, Fernanda Martins Lopes, Alfeu Zanotto-Filho, Marilda da Cruz Fernandes, Jose Claudio Fonseca Moreira, and Emily Shacter.