ABSTRACT
Introduction: 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.
Areas covered: 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.
Expert opinion: 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.
Article highlights
The combined knowledge on tumor microenvironment and molecular biomarkers associated with the development of lung carcinogenesis allows the design of more specific and accurate therapy, by targeting mutated key regulatory pathways.
RNAi-based therapeutics represents a promising and relevant strategy to overcome the problems associated with the available conventional treatments, such as chemotherapy and radiotherapy.
The success of RNAi-based therapeutics relies on the structure and properties of the developed nanocarriers, which determine the efficient delivery of the therapeutic RNAi molecule to the target tissue.
The main nanocarriers used in RNAi-based therapy to treat lung cancer are liposomes, polymeric micelles, metal-based nanosystems, dendrimers, and polymeric and lipid nanoparticles.
The functionalization of the nanocarrier enables a specific and targeted therapy to lung cancer cells, avoiding side effects and off-target risks and surpassing the biological and biochemical barriers associated with the delivery of RNAi molecules.
The success of RNAi-based therapeutics for lung cancer in animal models supports the translation to clinical trials and explains the growing interest in theranosis systems exhibiting advanced performances in diagnosis and therapy.
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.