RNAi-based therapeutics for lung cancer: biomarkers, microRNAs, and nanocarriers

  • Mariana Magalhães, Carmen Alvarez-Lorenzo, Angel Concheiro, Ana Figueiras, Ana Cláudia Santos, Francisco Veiga
  • Expert Opinion on Drug Delivery, September 2018, Taylor & Francis
  • DOI: 10.1080/17425247.2018.1517744

RNAi-based therapeutics for lung cancer: biomarkers, microRNAs, and nanocarriers

What is it about?

'Despite the current advances in the discovery of the lung cancer biomarkers and, consequently, in the diagnosis, this pathology continues to be the primary cause of cancer-related death worldwide. In most cases, the illness is diagnosed in an advanced stage, which limits the current treatment options available and reduces the survival rate. Therefore, RNAi-based therapy arises as a promising option to treat lung cancer. This review provides an overview on the exploitation of lung cancer biology to develop RNAi-based therapeutics to be applied in the treatment of lung cancer. Furthermore, the review analyzes the main nanocarriers designed to deliver RNAi molecules and induce antitumoral effects in lung cancer, and provides updated information about current RNAi-based therapeutics for lung cancer in clinical trials. RNAi-based therapy uses nanocarriers to perform a targeted and efficient delivery of therapeutic genes into lung cancer cells, by taking advantage of the known biomarkers in lung cancer. These therapeutic genes are key regulatory molecules of crucial cellular pathways involved in cell proliferation, migration, and apoptosis. Thereby, the characteristics and functionalization of the nanocarrier and the knowledge of lung cancer biology have direct influence in improving the therapeutic effect of this therapy.'

Why is it important?

'The discovery of crucial misexpressed genes in lung cancer allows a better understanding about the tumor microenvironment and the biomarkers that are a genetic fingerprint of this cancer. These biomarkers provide relevant knowledge to start the development of targeted therapies, overcoming the side effects and the development of resistances associated with the conventional treatments. As analyzed in this review, gene therapy and RNAi-based drugs have been considered as promising and exciting new approaches to treat lung cancer. These therapies may enable more specific and efficient targeted treatments through the delivery of therapeutic genes that are involved in mutated pathways associated to tumorigenesis. The advances made in RNAi-based formulation, in terms of transport and delivery efficiency, have attracted the interest of pharmaceutical companies to use these therapies in the treatment of several types of cancer; some clinical trials to treat lung cancer are already ongoing.'

Perspectives

Mariana Magalhães
University of Coimbra

'In the next decade, we foresee a strong research effort in the development of nanodelivery systems designed ad hoc to the peculiarities of RNAi-based therapeutic molecules, with a special attention to the delivery pathways and the combination of diagnosis elements and synergistic drugs. In which exosomes appear as a resourceful tool to improve lung cancer prognosis and diagnosis, while can also be used as efficient and biocompatible nanosystems in RNAi-based therapeutic approaches. The positive outcomes in the progress of RNAi-based therapeutics will pave the way to more clinical trials and thus more chances to achieve the clinical arena.'

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http://dx.doi.org/10.1080/17425247.2018.1517744

The following have contributed to this page: Mariana Magalhães and Dr Carmen Alvarez-Lorenzo