20/07/2016 - Press release
Lung cancer is the most deadly cancer in the world, causing more than one and a half million deaths a year. The most common subtype of lung cancer is adenocarcinoma. The presence of other underlying conditions, such as chronic obstructive pulmonary disease (COPD), which is also responsible for a high mortality rate in industrialised regions, increases the risk of developing it. Despite recent progress in therapeutic strategies for combatting this disease, the majority of patients who are diagnosed do not survive for more than five years. It is a cancer that can develop silently for many months and, in some cases, the symptoms can be confused with other diseases, such as the already-mentioned COPD. This is why it is usually diagnosed in very advanced stages. To all these impediments, it is necessary to add the difficulty of finding an appropriate treatment for each patient, since there is a high level of resistance to currently-used drugs.
The team of scientists led by Esther Barreiro, a researcher at the Hospital del Mar Medical Research Institute (IMIM) and a lecturer at Pompeu Fabra University, has carried out a study on mice to determine the improvements that can be obtained by combining various treatments for "non-small cell" lung cancer, the group to which adenocarcinoma belongs.
The drug bortezomib is widely used in the treatment of multiple myeloma and certain types of lymphoma. It acts by inhibiting proteasomes, cell organelles that are responsible for removing residual proteins. Despite being widely used, bortezomib is not effective if administered on its own. However, previous studies have shown that if you also inhibit other pathways that promote tumour growth, tumour death is achieved and the cell proliferation that promotes tumour growth is also halted.
MAPK and NF-κβ are two very important protein complexes in gene regulation. Previous research has demonstrated that they play a crucial role in cancer development, being involved in processes such as cell proliferation, inhibition of cell death, inflammation, vascular regeneration, and metastasis. In fact, NF-κβ activation is considered a marker for many types of cancers, including lung cancer.
Using this knowledge, Barreiro's team decided to combine bortezomib with antioxidants as well as MAPK and NF-κβ inhibitors. The results show improvements in all cases with the exception of antioxidants. In the case of MAPK and NF-κβ inhibitors there was a reduction in both tumour size and the loss of muscle mass linked to the cancer.
"The NF-κβ inhibitors and MAPK reduced the size of tumours through various biological mechanisms, including reducing the levels of oxidative stress and inflammation, probably leading to increased tumour degradation, as well as decreased cell proliferation", comments Barreiro. "These drugs may help improve the anti-tumoural activity of certain therapeutic strategies that are used in the treatment of non-small cell lung cancers."
Mateu-Jimenez M, Fermoselle C, Rojo F, Mateu J, Peña R, Urtreger AJ, Diament MJ, de Kier Joffé ED, Pijuan L, de Herreros AG, Barreiro E. Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology. Current Pharmaceutical Design, June 2016.