Abstract
Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.
Highlights
Lung cancer (LC) is recognized as the second most diagnosed type of cancer and the leading cause of cancer-related deaths globally [1]
We present the different molecular mechanisms of Drug resistance (DR) in LC and discuss the use of several types of nanocarriers to improve the chemotherapeutic outcome after treatment of drug resistant LC with anticancer drugs
The results showed that the combination therapy achieved a higher in vitro cytotoxicity result in both cell lines by oncogene dose-dependently reducing Kras, P-gp, and c-Myc, expression while improving p53 genetic modulation in drug-resistant cells
Summary
Lung cancer (LC) is recognized as the second most diagnosed type of cancer and the leading cause of cancer-related deaths globally [1]. Recent studies outlined how novel nano delivery systems could be prepared to exploit current TME hindrances in LC, such as the acidic nature of the microenvironment, increased accumulation of reactive oxygen species (ROS), expression of unique antigens at the tumor site, activation of immunogenic tissue as an immunomodulatory therapy, or external stimuli-triggered drug release, among others, achieving a relatively higher targeted activity in the tumor cell than with conventional therapy [33–37]. The NPs-based immunotherapy showed a significant reduction in the effective doses of volasertib and the PD-L1 antibody by five-fold in a metastatic lung in vivo tumor model by actively mediating CD8+ T cells, allowing the immune cells to induce their cytotoxic activity on the cancer cells These results clearly demonstrate the influence of targeting the TME on improving the clinical outcomes of current therapy [41]. Exploiting the molecular pathways and interactions that govern the TME could potentially enhance the current approach to therapy using a novel nano drug delivery systems (DDS)
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