Can the Synergy of Microneedles Technology and PROTACs Revolutionize Lip Oral Cavity Cancer Treatment?

Lip and oral cavity cancer continue to pose a significant clinical challenge, with current treatment strategies often encountering obstacles such as inefficient drug targeting, systemic toxicity, and the development of drug resistance. According to GLOBOCAN ۲۰۲۰, there were an estimated ۳۷۷,۷۱۳ new cases of lip and oral cavity cancer globally, resulting in ۱۷۷,۷۵۷ deaths, highlighting its severe impact on global health. Cancer is a complex and heterogeneous condition that often necessitates multi-pronged treatment strategies to achieve optimal therapeutic results. Given the limitations of monotherapies, especially in overcoming the intricate biological signaling pathways and drug resistance, there is a growing focus on combination therapies. This study introduces a novel hypothesis: utilizing the synergy between microneedles (MNs) and PROteolysis-Targeting Chimeras (PROTACs) for the treatment of lip and oral cavity cancer. Traditional inhibitors primarily function by binding to active sites to inhibit target proteins, but they are often ineffective against undruggable targets like transcription factors, scaffolding proteins, and non-enzymatic proteins. PROTACs represent an innovative approach for degrading disease-associated proteins. However, current PROTAC technologies face challenges such as poor solubility and inadequate organ-specific targeting, limiting their overall effectiveness as therapeutics. In addition, PROTACs are capable of degrading proteins in both cancerous and normal cells, and their catalytic activity can potentially lead to excessive depletion of the target protein, which may result in toxic side effects. Therefore, a more localized application of PROTAC technology could mitigate many of these adverse effects. One promising approach is the use of MNs to regulate PROTAC activity, enhancing their selectivity to specific tissues or sites. Emerging technologies, such as MNs and PROTACs, offer innovative solutions to these issues by enabling localized drug delivery and selectively degrading cancer-associated proteins. The field of medical diagnosis and treatment is undergoing a potential paradigm shift with the advancement of MNs technology. MNs provide a minimally invasive technique for localized, sustained drug delivery, significantly reducing off-target effects and improving patient adherence. When combined with PROTACs, which promote the selective degradation of oncogenic proteins through the ubiquitin-proteasome pathway, this approach aims to achieve precise and efficient degradation of tumor-promoting proteins within the tumor microenvironment. This study will explore the synergistic potential of combining microneedle-based delivery systems with PROTACs, assessing their pharmacokinetics, tumor-targeting capabilities, and overall therapeutic efficacy in lip and oral cavity cancer. Preliminary results indicate that this combination could enhance drug bioavailability, reduce systemic side effects, and specifically target cancer cells, thereby minimizing drug resistance and the risk of cancer recurrence. We propose the localized, targeted delivery of PROTACs to tumor sites using MNs patches. This study emphasizes the importance of integrating cutting-edge technologies to advance cancer treatment, particularly highlighting the potential of MNs and PROTACs to revolutionize the management of lip and oral cavity cancer. If successful, this combinatorial approach could represent a significant breakthrough in the treatment of this challenging cancer type.

کلیدواژه ها:

Lip Oral Cavity Cancer therapy ، microneedles (MNs) ، PROteolysis-Targeting Chimeras (PROTACs)