Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013-2023).

Matrix metalloproteinases (MMPs) are identifiable members of proteolytic enzymes that can degrade a wide range of proteins in the extracellular matrix (ECM). MMPs can be categorized into six groups based on their substrate specificity and structural differences: collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, and membrane-type MMPs. MMPs have been linked to a wide variety of biological processes, such as cell transformation and carcinogenesis. Over time, MMPs have been evaluated for their role in cancer progression, migration, and metastasis. Accordingly, various MMPs have become attractive therapeutic targets for anticancer drug development. The first generations of broad-spectrum MMP inhibitors displayed effective inhibitory activities but failed in clinical trials due to poor selectivity. Thanks to the evolution of X-ray crystallography, NMR analysis, and homology modeling studies, it has been possible to characterize the active sites of various MMPs and, consequently, to develop more selective, second-generation MMP inhibitors. In this review, we summarize the computational and synthesis approaches used in the development of MMP inhibitors and their evaluation as potential anticancer agents.

Respiratory tract infection-induced asthma exacerbations in adults with asthma: assessing predictors and outcomes.

Objective: To evaluate clinical and economic burden associated with respiratory tract infection (RTI)-induced asthma exacerbations and to identify risk factors associated with these exacerbations. Factors associated with these exacerbations are understudied and little information is available about consequent expenditures. Methods: In this retrospective case-control study, medical records and pharmacy data in King Abdullah University Hospital in Northern Jordan were reviewed for adults with asthma aged 40 years and older, over the period 2013-2016. Cases of RTI-induced asthma exacerbations were identified, and controls were selected randomly from asthmatic adults who did not experience any RTI-induced asthma exacerbation during the same period. Independent-samples t-tests and chi-square tests were conducted to compare patient characteristics of cases and controls. Predictors of RTI-induced asthma exacerbations and the resultant complications were evaluated using multivariable logistic regression. Multivariable regression on log-transformed charges was used to predict expenditures of these exacerbations. Results: A total of 137 cases and 548 controls were identified. Using inhaled corticosteroid + long-acting beta-agonists (ICS + LABA) was significantly associated with lower odds of RTI-induced asthma exacerbations (OR = 0.4; 95% CI, 0.21-0.77; p = 0.006), and lower odds of resultant serious complications (OR = 0.23; 95% CI, 0.07-0.69; p = 0.009), compared to being untreated with any asthma maintenance treatment. Asthma severity and co-morbidities were associated with increased susceptibility to these exacerbations. The average charges of RTI-induced asthma admissions and outpatient exacerbations were 1042.9 JD ($1471.0) and 81.1 JD ($114.4), respectively. Conclusions: ICS + LABA, asthma severity and co-morbidities appeared to affect the clinical and economic burden associated with RTI-induced asthma exacerbations. Efforts to prevent these exacerbations in patients with risk factors are warranted.