RESUMO
Drug repurposing is a strategy to discover new therapeutic uses for existing drugs, which have well-established toxicity profiles and are often more affordable. This approach has gained significant attention in recent years due to the high costs and low success rates associated with traditional drug development. Drug repositioning offers a more time- and cost-effective path for identifying new treatments. Several FDA-approved non-chemotherapy drugs have been investigated for their anticancer potential. Among these, anthelmintic benzimidazoles (such as albendazole, mebendazole, and flubendazole) have garnered interest due to their effects on microtubules and oncogenic signaling pathways. Blood cancers, which frequently develop resistance and have high mortality rates, present a critical need for effective therapies. This review highlights the recent advances in repurposing benzimidazoles for blood malignancies. These compounds induce cell cycle arrest, differentiation, tubulin depolymerization, loss of heterozygosity, proteasomal degradation, and inhibit oncogenic signaling to exert their anticancer effects. We also discuss current limitations and strategies to overcome them, emphasizing the potential of combining benzimidazoles with standard therapies for improved treatment of hematological cancers.
RESUMO
PURPOSE OF REVIEW: The intestinal microbiome plays a strong, complementary role in the development and integrity of the intestinal epithelium. This biology is crucial for intestinal adaptation, particularly after the mucosal insults that lead to short bowel syndrome (SBS). The purpose of this review is to discuss relationships between the intestinal microbiota and the physiology of intestinal adaptation. RECENT FINDINGS: We will address interactions between the intestinal microbiome and nutritional metabolism, factors leading to dysbiosis in SBS, and common compositional differences of the gut microbiome in SBS patients as compared to healthy controls. We will also discuss novel opportunities to expand diagnostic and therapeutic interventions in this population, by using our knowledge of the microbiome to manipulate luminal bacteria and study their resultant metabolites. As microbial therapeutics advance across so many fields of medicine, this review is timely in its advocacy for ongoing research that focuses on the SBS population.Our review will discuss 4 key areas: 1) physiology of the intestinal microbiome in SBS, 2) clinical and therapeutic insults that lead to a state of dysbiosis, 3) currently available evidence on microbiome-based approaches to SBS management, and 4) opportunities and innovations to inspire future research. SUMMARY: The clinical implications of this review are both current, and potential. Understanding how the microbiome impacts intestinal adaptation and host physiology may enhance our understanding of why we experience such clinical variability in SBS patients' outcomes. This review may also expand clinicians' understanding of what 'personalized medicine' can mean for this patient population, and how we may someday consider our nutritional, therapeutic, and prognostic recommendations based on our patients' host, and microbial physiology.