Leishmaniasis is a complex protozoan infectious disease and, associated with malnutrition, poor health services and unavailability of prophylactic control measures, neglected populations are particularly affected. Current drug regimens are outdated and associated with some drawbacks, such as cytotoxicity and resistance, and the development of novel, efficacious and less toxic drug regimens is urgently required. In addition, leishmanial pathogenesis is not well established or understood, and a prophylactic vaccine is an unfulfilled goal. Human kinetoplastid protozoan infections, including leishmaniasis, have been neglected for many years, and in an attempt to overcome this situation, some new drug targets were recently identified, enabling the development of new drugs and vaccines. Compounds from new drug classes have also shown excellent antileishmanial activities, some of the most promising ones included in clinical trials, and could be a hope to control the disease burden of this endemic disease in the near future. In this review, we discuss the limitations of current control methods, explore the wide range of compounds that are being screened and identified as antileishmanial drug prototypes, summarize the advances in identifying new drug targets aiming at innovative treatments and explore the state-of-art vaccine development field, including immunomodulation strategies.
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http://dx.doi.org/10.1039/d1md00362c | DOI Listing |
Expert Opin Biol Ther
January 2025
OU Stephenson Cancer Center, Oklahoma City.
Introduction: Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.
View Article and Find Full Text PDFClin Transl Sci
January 2025
Global Biometrics and Data Management, Pfizer Research and Development, New York, New York, USA.
The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model-Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as pharmacokinetics and pharmacodynamics. Artificial intelligence (AI), encompassing techniques such as machine learning, deep learning, and Generative AI, offers powerful tools and algorithms to efficiently identify meaningful patterns, correlations, and drug-target interactions from big data, enabling more accurate predictions and novel hypothesis generation.
View Article and Find Full Text PDFJ Clin Med
December 2024
Pharmacy Department, Institut Català Oncologia (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet Llobregat, 08908 Barcelona, Spain.
Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10-26.
View Article and Find Full Text PDFJ Clin Med
December 2024
Division of Ophthalmology, Department of Surgery, UMass Chan-Lahey School of Medicine, Burlington, MA 01805, USA.
Personalizing the management of neovascular age-related macular degeneration (nAMD) poses significant challenges for practicing retina specialists and their patients. This commentary addresses some of these complexities, particularly those that arise in the context of an expanding array of intravitreal agents targeting vascular endothelial growth factor (VEGF) and related retinal disease targets. Many of these newer agents approved by the Food and Drug Administration (FDA) for the treatment of nAMD have labeling that indicates that they can provide non-inferior visual outcomes when compared head-to-head with previously available treatments and can be used at significantly extended dosing intervals in some patients.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Background/objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness.
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