Nanotechnology-based delivery systems to overcome drug resistance in cancer.

Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics. Multidrug resistance (MDR) in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure. There have been successes in the development of cancer nanomedicine to overcome MDR; however, relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer. This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells. Here, we discuss the advances, types of nanomedicines, and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.

Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.

Breast cancer, a complex and varied disease, has four distinct subtypes based on estrogen receptor and human epidermal growth factor receptor 2 (HER2) levels, among which a significant subtype known as HR+/HER2-breast cancer that has spurred numerous research. The prevalence of breast cancer and breast cancer-related death are the most serious threats to women's health worldwide. Current progress in treatment strategies for HR+/HER2-breast cancer encompasses targeted therapy, endocrine therapy, genomic immunotherapy, and supplementing traditional methods like surgical resection and radiotherapy. This review article summarizes the current epidemiology of HR+/HER2-breast cancer, introduces the classification of HR+/HER2-breast cancer and the commonly used treatment methods. The mechanisms of action of various drugs, including targeted therapy drugs and endocrine hormone therapy drugs, and their potential synergistic effects are deeply discussed. In addition, clinical trials of these drugs that have been completed or are still in progress are included.

The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options.

Antimicrobial peptides for combating drug-resistant bacterial infections.

The problem of drug resistance due to long-term use of antibiotics has been a concern for years. As this problem grows worse, infections caused by multiple bacteria are expanding rapidly and are extremely detrimental to human health. Antimicrobial peptides (AMPs) are a good alternative to current antimicrobials with potent antimicrobial activity and unique antimicrobial mechanisms, which have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Currently, researchers have conducted clinical investigations on AMPs for drug-resistant bacterial infections while integrating new technologies in the development of AMPs, such as changing amino acid structure of AMPs and using different delivery methods for AMPs. This article introduces the basic properties of AMPs, deliberates the mechanism of drug resistance in bacteria and the therapeutic mechanism of AMPs. The current disadvantages and advances of AMPs in combating drug-resistant bacterial infections are also discussed. This article provides important insights into the research and clinical application of new AMPs for drug-resistant bacterial infections.

Amivantamab: a monoclonal EGFR-MET bispecific antibody for EGFR exon 20 insertion in non-small cell lung cancer.

The U.S. Food and Drug Administration (FDA) first approved amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal--epithelial transition factor (MET) bispecific antibody, in May 2021, to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an insertion mutation in exon 20 of EGFR. The approval of amivantamab represents a targeted therapy for this subtype of advanced NSCLC. In contrast to other drugs that inhibit the tyrosine kinase activity in the protein, EGFR, amivantamab has efficacy in inhibiting EGFR and MET. In this article, we summarize the development of therapeutic drugs for NSCLC, discuss the mechanism of action of amivantamab, review data from clinical trials with amivantamab and suggest future lines of research.

The Roles of Exosomal microRNAs in Diffuse Large B-Cell Lymphoma: Diagnosis, Prognosis, Clinical Application, and Biomolecular Mechanisms.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers. Recently, exosomal miRNAs have been approved as novel biomarkers in DLBCL due to their potential involvement in lymphomagenesis. Material and Methods: We conducted an investigation on the potential role of exosomal miRNAs as diagnostic, prognostic, and predictive biomarkers in DLBCL in the PubMed, Scopus, and Web of Science search engines. We searched by using a combination of keywords, such as diffuse large B-cell lymphoma, DLBCL, miRNA, microRNA, miR, exosome, exosomes, exosomal, extracellular vesicles, EVs, and secretome. Then, search results were narrowed based on specific inclusion and exclusion criteria. Results: Twelve articles were eligible for our systematic reviews. Among them, nine discussed diagnostic biomarkers, three considered prognostic significance, four evaluated therapeutic efficacy, two studies were conducted in vitro, and three assessed molecular pathways associated with these exosomal miRNAs in DLBCL. Discussion: According to our systematic review, exosomal miRNAs are not only useful for diagnosis and prognosis in DLBCL but are also promising therapeutic tools and predictors of response to therapy. Although promising results so far, more research is required to develop innovative biomarkers.

Drug resistance: from bacteria to cancer.

The phenomenon of drug resistance has been a hindrance to therapeutic medicine since the late 1940s. There is a plethora of factors and mechanisms contributing to progression of drug resistance. From prokaryotes to complex cancers, drug resistance is a prevailing issue in clinical medicine. Although there are numerous factors causing and influencing the phenomenon of drug resistance, cellular transporters contribute to a noticeable majority. Efflux transporters form a huge family of proteins and are found in a vast number of species spanning from prokaryotes to complex organisms such as humans. During the last couple of decades, various approaches in analyses of biochemistry and pharmacology of transporters have led us to understand much more about drug resistance. In this review, we have discussed the structure, function, potential causes, and mechanisms of multidrug resistance in bacteria as well as cancers.

Establishment and Characterization of an Irinotecan-Resistant Human Colon Cancer Cell Line.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Irinotecan is widely used as a chemotherapeutic drug to treat CRC. However, the mechanisms of acquired resistance to irinotecan in CRC remain inconclusive. In the present study, we established a novel irinotecan-resistant human colon cell line to investigate the underlying mechanism(s) of irinotecan resistance, particularly the overexpression of ABC transporters. The irinotecan-resistant S1-IR20 cell line was established by exposing irinotecan to human S1 colon cancer cells. MTT cytotoxicity assay was carried out to determine the drug resistance profile of S1-IR20 cells. The drug-resistant cells showed about 47-fold resistance to irinotecan and cross-resistance to ABCG2 substrates in comparison with S1 cells. By Western blot analysis, S1-IR20 cells showed significant increase of ABCG2, but not ABCB1 or ABCC1 in protein expression level as compared to that of parental S1 cells. The immunofluorescence assay showed that the overexpressed ABCG2 transporter is localized on the cell membrane of S1-IR20 cells, suggesting an active efflux function of the ABCG2 transporter. This finding was further confirmed by reversal studies that inhibiting efflux function of ABCG2 was able to completely abolish drug resistance to irinotecan as well as other ABCG2 substrates in S1-IR20 cells. In conclusion, our work established an in vitro model of irinotecan resistance in CRC and suggested ABCG2 overexpression as one of the underlying mechanisms of acquired resistance to irinotecan. This novel resistant cell line may enable future studies to overcome drug resistance in vitro and improve CRC treatment in vivo.

Putrescine protects hulless barley from damage due to UV-B stress via H2S- and H2O2-mediated signaling pathways.

KEY MESSAGE: In hulless barley, H 2 S mediated increases in H 2 O 2 induced by putrescine, and their interaction enhanced tolerance to UV-B by maintaining redox homeostasis and promoting the accumulation of UV-absorbing compounds. This study investigated the possible relationship between putrescence (Put), hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) as well as the underlying mechanism of their interaction in reducing UV-B induced damage. UV-B radiation increased electrolyte leakage (EL) and the levels of malondialdehyde (MDA) and UV-absorbing compounds but reduced antioxidant enzyme activities and glutathione (GSH) and ascorbic acid (AsA) contents. Exogenous application of Put, H2S or H2O2 reduced some of the above-mentioned negative effects, but were enhanced by the addition of Put, H2S and H2O2 inhibitors. Moreover, the protective effect of Put against UV-B radiation-induced damage to hulless barley was diminished by DL-propargylglycine (PAG, a H2S biosynthesis inhibitor), hydroxylamine (HT, a H2S scavenger), diphenylene iodonium (DPI, a PM-NADPH oxidase inhibitor) and dimethylthiourea (DMTU, a ROS scavenger), and the effect of Put on H2O2 accumulation was abolished by HT. Taken together, as the downstream component of the Put signaling pathway, H2S mediated H2O2 accumulation, and H2O2 induced the accumulation of UV-absorbing compounds and maintained redox homeostasis under UV-B stress, thereby increasing the tolerance of hulless barley seedlings to UV-B stress.