Eighty-five percent of diagnosed cases of lung cancer are non-small cell lung cancer (NSCLC). In this group, 5% of patients show molecular alterations in the ALK gene involved in cell multiplication. The use of inhibitors against this oncogene - one of the most effective strategies against this type of cancer - has benefited many patients. But, is it possible to know if the treatment will be effective in all those affected?
Now, a study led by the University of Barcelona reveals that the functional assay dynamic BH3 profiling (DBP) can predict whether this treatment will be effective in these cancer patients and thus improve personalized therapies. This technique achieves with tumours something very similar to what an antibiogram achieves with a bacterial infection: determining which therapy will be most effective by testing it directly on living cells.
The technique, which helps to select the best drug for each patient, was patented in 2015 by the Dana-Farber Cancer Institute (Boston, United States) and its co-inventor is Joan Montero, professor at the UB's Faculty of Medicine and Health Sciences and at the Bioengineering, Biomaterials and Nanomedicine Networking Biomedical Research Centre (CIBER-BBN).
The new study, published in Nature's journal Cell Death and Disease , is led by Professor Joan Montero and its first author is researcher Fernando Martín, a member of the UB, the Institute for Bioengineering of Catalonia (IBEC) and CIBERBBN. Teams from the UB's Faculty of Physics, Hospital Clínic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Catalan Institute of Oncology (ICO) are also collaborating in the paper.
The study, conducted using animal models and patient biopsies, also reveals for the first time that the MCL-1 protein plays a key role in tumour resistance to this type of therapy. It also shows that molecules known as BH3 mimetics can improve the effect of cancer treatments by preventing tumour adaptations to inhibitors of anaplastic lymphoma protein kinase (ALK), one of the main treatments for this cancer.
Predicting the response of the most common lung cancer drugs
Each tumour is unique, and predicting the therapeutic response to non-small cell lung cancer is a breakthrough in personalized medicine. Given this challenge in biomedicine, the study confirms that the dynamic BH3 profiling technique has an excellent predictive capacity for tumour cell response to ALK inhibitors.
ALK inhibitors are used early in disease in patients with non-small cell lung cancer who show molecular alterations in this oncogene. Currently, four generations of ALK inhibitors have been developed with clinical efficacy superior to chemotherapy.
