HMGB1 Enhances Drug Resistance and Promotes In Vivo Tumor Growth of Lung Cancer Cells

Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year.

The treatment of advanced non-small cell lung cancer (NSCLC) may be changing, but the cisplatin-based doublet remains the foundation of treatment for the majority of patients with advanced NSCLC. In this respect, changes in practice to various aspects of cisplatin use, such as administration schedules and the choice of methods and frequency of monitoring for toxicities, have contributed to an incremental improvement in patient management and experience. Chemoresistance, however, limits the clinical utility of this drug in patients with advanced NSCLC. Better understanding of the molecular mechanisms of cisplatin resistance, identification of predictive markers and the development of newer, more effective and less toxic platinum agents is required. In addition to maximising potential benefits from advances in molecular biology and associated therapeutics, modification of existing cisplatin-based treatments can still lead to improvements in patient outcomes and experiences.

Cancer is a multifaceted disease comprising a combination of genetic, metabolic and signalling aberrations, which severely disrupt the normal homeostasis of cell growth and death. Many oncogenic events while promoting tumour development also increase the sensitivity of cells to cell death stimuli including chemotherapeutic drugs. As a result, tumour cells often acquire the ability to evade death by inactivating cell death pathways that normally function to eliminate damaged and harmful cells. The impairment of cell death function is also often the reason for the development of chemotherapeutic resistance encountered during treatment. It is therefore necessary to achieve a comprehensive understanding of existing cell death pathways and the relevant regulatory components involved, with the intention of identifying new strategies to kill cancer cells. This review provides an insightful overview of the common forms of cell death signalling pathways, the interactions between these pathways and the ways in which these pathways are deregulated in cancer. We also discuss the emerging therapies targeted at activating or restoring cell death pathways to induce tumour cell death, which are currently being tested in clinical trials.