Recent updates on the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors and resistance reversion strategies in lung cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have led to a substantial improvement in the prognosis of lung cancer patients by explicitly targeting the activating mutations within the EGFR. Initially, patients harboring tumors with EGFR mutations show progression-free survival and improvement in the response rates toward all-generation EGFR-TKIs; however, these agents fail to deliver the intended results in the long-term due to drug resistance. Therefore, it is necessary to recognize specific cardinal mechanisms that regulate the resistance phenomenon. Understanding the intricate mechanisms underlying EGFR-TKIs resistance in lung cancer could provide cognizance for more advanced targeted therapeutics. The present review features insights into current updates on the discrete mechanisms, including secondary or tertiary mutations, parallel and downstream signaling pathways, acquiring an epithelial-to-mesenchymal transition (EMT) signature, microRNAs (miRNAs), and epigenetic alterations, which lead to intrinsic and acquired resistance against EGFR-TKIs in lung cancer. In addition, this paper also reviews current possible strategies to overcome this issue using combination treatment of recently developed MET inhibitors, allosteric inhibitors or immunotherapies, transformation of EMT, targeting miRNAs, and epigenetic alterations in intrinsic and acquired EGFR-TKIs resistant lung cancer. In conclusion, multiple factors are responsible for intrinsic and acquired resistance to EGFR-TKIs and understanding of the detailed molecular mechanisms, and recent advancements in pharmacological studies are needed to develop new strategies to overcome intrinsic and acquired EGFR-TKIs resistance in lung cancer.     

Cost-Effective Production of TiO2 with 90-Fold Enhanced Photocatalytic Activity Via Facile Sequential Calcination and Ball Milling Post-Treatment Strategy

Titanium dioxide (TiO₂), the golden standard among the photocatalysts, exhibits a varying level of photocatalytic activities (PCA) amongst the synthetically prepared and commercially available products. For commercial applications, superior photoactivity and cost-effectiveness are the two main factors to be reckoned with. This study presents the development of simple, cost-effective post-treatment processes for a less costly TiO₂ to significantly enhance the PCA to the level of expensive commercial TiO₂ having demonstrated superior photoactivities. We have utilized sequential calcination and ball milling (BM) post-treatment processes on a less-costlier KA100 TiO₂ and demonstrated multi-fold (nearly 90 times) enhancement in PCA. The post-treated KA100 samples along with reference commercial samples (P25, NP400, and ST01) were well-characterized by appropriate instrumentation and evaluated for the PCA considering acetaldehyde photodegradation as the model reaction. Lattice parameters, phase composition, crystallite size, surface functionalities, titanium, and oxygen electronic environments were evaluated. Among post-treated KA100, the sample that is subjected to sequential 700 °C calcination and BM (KA7-BM) processes exhibited 90-fold PCA enhancement over pristine KA100 and the PCA-like commercial NP400 (pure anatase-based TiO₂). Based on our results, we attribute the superior PCA for KA7-BM due to the smaller crystallite size, the co-existence of mixed anatase-srilankite-rutile phases, and the consequent multiphase heterojunction formation, higher surface area, lattice disorder/strain generation, and surface oxygen environment. The present work demonstrates a feasible potential for the developed post-treatment strategy towards commercial prospects.     

Nanoparticle drug delivery to target breast cancer brain metastasis: Current and future trends

Breast cancer brain metastasis (BCBM) is rapidly becoming an impediment to continuing survival gains seen in breast cancer patients. Drug delivery across the blood-brain barrier is the main issue hindering systemic therapy against BCBM. This review details recent advances in nanoparticle (NP) drug delivery systems to target BCBM. Their primary benefits are: enhanced circulating and intra-BCBM drug biodistribution, BCBM targeting through NP functionalization, opportunities for gene manipulation and their theragnostic applications. Multiple NPs have been synthesized to deliver therapeutic HER2 blockade, which is particularly important given HER2-positive breast cancer's tendency to form BCBM. Finally, we review the clinical context in which NP-based therapeutics have been investigated in BCBM patients. While a breakthrough in improving patient outcomes remain awaited, these clinical trials represent positive steps in the changing attitude towards BCBM as a treatable illness. Although multiple challenges remain in the clinical translation of BCBM-directed NP therapies, ongoing research in the field offers promising avenues for novel targeting of this devastating disease.     

The impact of HIV antiretroviral treatment perception on risky sexual behaviour in Botswana: a short report

The aim of this article is to investigate the impact of ART perception on risky sexual behaviours in Botswana. Using binary logistic regression analysis controlling for individual characteristics, the results tend to support the hypothesis that ART misconceptions do not necessarily increase risky sexual behaviours. In particular, the study findings suggest the belief that ARVs cure HIV and AIDS and that people on ARVs should not always use condoms do not necessarily lead to increased risky sexual behaviours, particularly among women. Gender differentials exist in the perceived sexual risk resulting from the use of ART. Risky sexual behaviours increase for women who, wrongly, believed that ARVs cure HIV and AIDS and people on ARVs should not always use condoms. Although there is evidence to suggest ART perceptions do not necessarily lead to increased risky sexual behaviours, HIV and AIDS prevention programmes are needed to strengthen their information, education and communication intervention component that can address misconceptions about ART treatment and provide correct information that is gender-appropriate.