Current Medicinal Chemistry - Volume 27, Issue 34, 2020

The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor-infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the Pattern Recognition Receptors (PRRs), proteins which detect pathogenic and damageassociated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like Receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN Genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-Ilike Receptors (RLRs) and NOD-like Receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.

Background: Ovarian cancer is the second most common gynecologic malignancy, accounting for approximately 220,000 deaths annually worldwide. Despite radical surgery and initial high response rates to platinum- and taxane-based chemotherapy, most patients experience a relapse, with a median progression-free survival of only 18 months. Overall survival is approximately 30% at 5 years from the diagnosis. In comparison, patients out from breast cancer are more than 80 % after ten years from the disease discovery. In spite of a large number of published fundamental and applied research, and clinical trials, novel therapies are urgently needed to improve outcomes of the ovarian cancer. The success of new drugs development in ovarian cancer will strongly depend on both fully genomic disease characterization and, then, availability of biomarkers able to identify women likely to benefit from a given new therapy. Methods: In this review, the focus is given to describe how complex is the diseases under the simple name of ovarian cancer, in terms of cell tumor types, histotypes, subtypes, and specific gene mutation or differently expressed in the tumor with respect the healthy ovary. The first- and second-line pharmacological treatment clinically used over the last fifty years are also described. Noteworthy achievements in vitro and in vivo tested new drugs are also summarized. Recent literature related to up to date ovarian cancer knowledge, its detection by biomarkers and chemotherapy was searched from several articles on Pubmed, Google Scholar, MEDLINE and various Governmental Agencies till April 2019. Results: The papers referenced by this review allow a deep analysis of status of the art in the classification of the several types of ovarian cancer, the present knowledge of diagnosis based on biomarkers and imaging techniques, and the therapies developed over the past five decades. Conclusion: This review aims at stimulating more multi-disciplinary efforts to identify a panel of novel and more specific biomarkers to be used to screen patients for a very early diagnosis, to have prognosis and therapy efficacy indications. The desired final goal would be to have available tools allowing to reduce the recurrence rate, increase both the disease progression free interval and of course the overall survival at five years from the diagnosis that today is still very low.

Background: Immunotherapy for cancer includes Chimeric Antigen Receptor (CAR)-T cells, CAR-natural Killer (NK) cells, PD1, and the PD-L1 inhibitor. However, the proportion of patients who respond to cancer immunotherapy is not satisfactory. Concurrently, nanotechnology has experienced a revolution in cancer diagnosis and therapy. There are few clinically approved nanoparticles that can selectively bind and target cancer cells and incorporate molecules, although many therapeutic nanocarriers have been approved for clinical use. There are no systematic reviews outlining how nanomedicine and immunotherapy are used in combination to treat cancer. Objective: This review aims to illustrate how nanomedicine and immunotherapy can be used for cancer treatment to overcome the limitations of the low proportion of patients who respond to cancer immunotherapy and the rarity of nanomaterials in clinical use. Methods: A literature review of MEDLINE, PubMed / PubMed Central, and Google Scholar was performed. We performed a structured search of literature reviews on nanoparticle drug-delivery systems, which included photodynamic therapy, photothermal therapy, photoacoustic therapy, and immunotherapy for cancer. Moreover, we detailed the advantages and disadvantages of the various nanoparticles incorporated with molecules to discuss the challenges and solutions associated with cancer treatment. Conclusion: This review identified the advantages and disadvantages associated with improving health care and outcomes. The findings of this review confirmed the importance of nanomedicinecombined immunotherapy for improving the efficacy of cancer treatment. It may become a new way to develop novel cancer therapeutics using nanomaterials to achieve synergistic anticancer immunity.

Mitochondria are key players with a multi-functional role in many vital cellular processes, such as energy metabolism, redox regulation, calcium homeostasis, Reactive Oxygen Species (ROS) as well as in cell signaling, survival and apoptosis. These functions are mainly regulated through important enzyme signaling cascades, which if altered may influence the outcome of cell viability and apoptosis. Therefore some of the key enzymes that are vital for these signaling pathways are emerging as important targets for new anticancer agent development. Mitocans are compounds aimed at targeting mitochondria in cancer cells by altering mitochondrial functions thus causing cell growth inhibition or apoptosis. This review summarizes the till present known classes of mitocans, their mechanism of action and potential therapeutic use in different forms of cancer.

Tumor metastasis is a significant cause of malignant cancer-related death. Therefore, inhibiting tumor metastasis is an effective means of treating malignant tumors. Increasing our understanding of the molecular mechanisms that govern tumor metastasis can reveal new anti-cancer targets. This article will discuss the breakthroughs in this area and the corresponding recent developments in anti-cancer drug discovery.

Background: Injectable hydrogels are a thermo-responsive system based on biomaterials. Injectable hydrogels have been broadly investigated mainly as vehicles or scaffolds of therapeutic agents that include drugs, proteins, cells, and bioactive molecules among others, utilized in the treatment of diseases such as cancers and the repair and regeneration of tissues. Results: There are several studies that have described the multiple features of hydrogels. However, the main aspect that breaks the paradigm in the application of hydrogels is the thermoresponsiveness that some of them have, which is an abrupt modification in their properties in response to small variations in temperature. For that reason, the thermo-responsive hydrogels with the unique property of sol-gel transition have received special attention over the past decades. These hydrogels show phase transition near physiological human body temperature. This feature is key for being applied in promising areas of human health-related research. Conclusion: The purpose of this study is the overview of injectable hydrogels and their latest advances in medical applications including bioactive compound delivery, tissue engineering, and regenerative medicine.

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Toll-like Receptors (TLRs) are members of pattern recognition receptors and serve a pivotal role in host immunity. TLRs response to pathogen-associated molecular patterns encoded by pathogens or damage-associated molecular patterns released by dying cells, initiating an inflammatory cascade, where both beneficial and detrimental effects can be exerted. Accumulated evidence has revealed that TLRs are closely associated with various kidney diseases but their roles are still not well understood. This review updated evidence on the roles of TLRs in the pathogenesis of kidney diseases including urinary tract infection, glomerulonephritis, acute kidney injury, transplant allograft dysfunction and chronic kidney diseases.