Personalized and Precision Medicine Journal

Abstract Drug resistance is a major obstacle in the effective treatment of cancer, severely impacting patient outcomes and complicating therapeutic strategies. The development of resistance is multifactorial, involving a combination of genetic and epigenetic changes within cancer cells, alterations in drug metabolism, increased DNA repair mechanisms, overexpression of drug efflux pumps, and complex interactions with the tumor microenvironment. These factors work synergistically to render traditional chemotherapy and targeted therapies less effective over time.
Recent advances in molecular biology, particularly next-generation sequencing and the CRISPR-Cas9 gene-editing tool, have significantly enhanced our understanding of the underlying mechanisms driving resistance. These technologies have enabled researchers to identify novel genetic mutations and signaling pathways that cancer cells exploit to evade treatment, offering new potential targets for therapeutic intervention. Additionally, the dynamic role of the tumor microenvironment, including immune cells, stromal cells, and extracellular matrix components, has emerged as a key factor influencing drug resistance, further complicating treatment strategies.
To address these challenges, several innovative therapeutic approaches are being explored. Combination therapies, which involve the use of multiple drugs targeting different pathways simultaneously, hold promise in overcoming resistance by attacking cancer cells from multiple fronts. Immunotherapy, which harnesses the body's immune system to target cancer cells, is also showing significant potential in resistant cancers. Furthermore, nanomedicine, which uses nanoparticles to deliver drugs directly to tumors, may improve drug efficacy and minimize resistance.
Despite these advancements, much remains to be done. Ongoing research focused on identifying reliable biomarkers, developing personalized medicine approaches, and understanding the intricate relationship between cancer cells and their microenvironment is essential. This review aims to provide a comprehensive overview of the current state of knowledge regarding drug resistance in cancer, emerging therapeutic strategies, and future research directions in this critical field.

Abstract Drug resistance in cancer is a major challenge to properly treating malignancy. Therapies aimed at proteins involved in cancer development may become less effective due to acquired resistance to medications, often resulting from mutations as well as heightened expression of the targeted proteins. Posttranslational modifications (PTMs) like as phosphorylation, methylation, ubiquitination, and acetylation are crucial for regulating protein expression levels. PROTACs are engineered to selectively degrade a specific protein of interest (POI) by ubiquitination, resulting in a regulated decrease in the POI’s expression. PROTACs show great potential in targeting hitherto untargetable proteins, such as various transcription factors. PROTACs enhance antitumor immune therapy by specifically modifying certain proteins. Although molecular therapies have advanced, lung cancer remains a major contributor to cancer-related mortality. The management of those with lung cancer is now limited by a lack of targeted therapy choices and the development of acquired drug resistance. Using the intracellular ubiquitin-proteasome system for directed protein breakdown might enhance individualized treatment for lung cancer patients. This study explores the rationale for using PROTAC therapy as an innovative specific therapy and the current advancements in PROTAC development for lung tumors.

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Approximately 25% of nonsmall-cell lung cancers have mutations in the EGFR gene, most of which occur in hotspot regions in exons 18, 19, 20, and 21. In-frame deletions in exon 19 (~50%) and the L858R point mutation in exon 21 (~40%) are associated with a favorable response to EGFR tyrosine kinase inhibitors. In this study, mutations of two exons of 19 and 21 in 50 lung cancer tumor samples were investigated by the sequence method. From 50 lung cancer patients, 8 (16%) patients had an L858R (c.2573T>G) mutation, 6 (12%) patients had deletion type 1a mutation, and one patient had deletion type 1b mutation. Examining the sequence of candidate genes associated with lung cancer can be very important in choosing the right treatment approach.