Current Topics in Medicinal Chemistry - Volume 23, Issue 30, 2023

As far as malignant tumors of the central nervous system are concerned, glioblastoma (GB) and neuroblastoma (NB) are the most prevalent, aggressive, and fatal forms in adult and pediatric populations, respectively. NB is the most prominent childhood extracranial compact neoplasm in pediatrics when the embryo develops from undifferentiated neural crest cells. Regarding malignant primary brain tumors, GB is the most lethal and difficult to treat. Currently, there are few effective treatments available for either condition. Research using zebrafish is relatively new in the field of animal cancer studies, and the first results show promise. In particular, integrated genomic investigations of NB and GB have revealed the potential of the zebrafish model in elucidating the roles of specific genetic changes in the development of this fatal childhood malignancy. Hence, this study examines the possibility of zebrafish as a model organism for discovering integrative medicines for these types of cancer. This model is an excellent animal model for study due to its transparency, ease of genetic modification, ethics and financial benefits, and preservation of the primary brain areas andbloodbrain barrier (BBB). This review provides recent developments in the zebrafish model of NB and GB to illustrate the benefits of using them in cancer studies as a model of the organism. This approach provides novel insights into delivering individualized treatment and enhancing outcomes for people coping with central nervous system malignancies.

Colorectal cancer (CRC) is a multifaceted and heterogeneous ailment that affects the colon or rectum of the digestive system. It is the second most commonly occurring form of cancer and ranks third in terms of mortality rate. The progression of CRC does not occur due to a single mutational event; rather, it is the result of the sequential and cumulative accumulation of mutations in key driver genes of signaling pathways. The most significant signaling pathways, which have oncogenic potential due to their deregulation, include Wnt/β-catenin, Notch, TGF-β, EGFR/MAPK, and PI3K/AKT pathways. Numerous drug target therapies have been developed to treat CRC using small molecule inhibitors, antibodies, or peptides. Although drug-targeted therapy is effective in most cases, the development of resistance mechanisms in CRC has raised questions about their efficacy. To overcome this issue, a novel approach to drug repurposing has come to light, which utilizes already FDA-approved drugs to treat CRC. This approach has shown some promising experimental results, making it a crucial avenue of research in the treatment of CRC.

Cancer is considered one of the deadliest diseases globally, and continuous research is being carried out to find novel potential therapies for myriad cancer types that affect the human body. Researchers are hunting for innovative remedies to minimize the toxic effects of conventional therapies being driven by cancer, which is emerging as pivotal causes of mortality worldwide. Cancer progression steers the formation of heterogeneous behavior, including self-sustaining proliferation, malignancy, and evasion of apoptosis, tissue invasion, and metastasis of cells inside the tumor with distinct molecular features. The complexity of cancer therapeutics demands advanced approaches to comprehend the underlying mechanisms and potential therapies. Precision medicine and cancer therapies both rely on drug discovery. In vitro drug screening and in vivo animal trials are the mainstays of traditional approaches for drug development; however, both techniques are laborious and expensive. Omics data explosion in the last decade has made it possible to discover efficient anti-cancer drugs via computational drug discovery approaches. Computational techniques such as computer-aided drug design have become an essential drug discovery tool and a keystone for novel drug development methods. In this review, we seek to provide an overview of computational drug discovery procedures comprising the target sites prediction, drug discovery based on structure and ligand-based design, quantitative structure-activity relationship (QSAR), molecular docking calculations, and molecular dynamics simulations with a focus on cancer therapeutics. The applications of artificial intelligence, databases, and computational tools in drug discovery procedures, as well as successfully computationally designed drugs, have been discussed to highlight the significance and recent trends in drug discovery against cancer. The current review describes the advanced computer-aided drug design methods that would be helpful in the designing of novel cancer therapies.

Cancer is responsible for high mortality rates worldwide, representing a serious health problem. In this sense, melanoma corresponds to the most aggressive type of skin cancer, being the cause of the highest death rates. Therapeutic strategies for the treatment of melanoma remain limited, with problems associated with toxicity, serious side effects, and mechanisms of resistance. The potential of natural products for the prevention and treatment of melanoma has been reported in different studies. Among these compounds, naphthoquinones (1,2-naphthoquinones and 1,4-naphthoquinones) stand out for their diverse pharmacological properties, including their antitumor activity. Thus, this review covers different studies found in the literature on the application of natural naphthoquinones targeting melanoma, providing information regarding the mechanisms of action investigated for these compounds. Finally, we believe that this review provides a comprehensive basis for the use of natural naphthoquinones against melanoma and that it may contribute to the discovery of promising compounds, specifically naphthoquinones, aimed at the treatment of this cancer.

Receptor tyrosine kinase (RTK) regulates multiple pathways, including Mitogenactivated protein kinases (MAPKs), PI3/AKT, JAK/STAT pathway, etc. which has a significant role in the progression and metastasis of tumor. As RTK activation regulates numerous essential bodily processes, including cell proliferation and division, RTK dysregulation has been identified in many types of cancers. Targeting RTK is a significant challenge in cancer due to the abnormal upregulation and downregulation of RTK receptors subfamily EGFR, FGFR, PDGFR, VEGFR, and HGFR in the progression of cancer, which is governed by multiple RTK receptor signalling pathways and impacts treatment response and disease progression. In this review, an extensive focus has been carried out on the normal and abnormal signalling pathways of EGFR, FGFR, PDGFR, VEGFR, and HGFR and their association with cancer initiation and progression. These are explored as potential therapeutic cancer targets and therefore, the inhibitors were evaluated alone and merged with additional therapies in clinical trials aimed at combating global cancer.

Cancer is one of the leading causes of death, and numerous methods have been tested and used to figure out an optimum way of treatment. Besides targeted therapy, immunotherapy has proven to be effective by controlling certain immune cells. Traditional cancer therapy is met with the consequences of adverse side effects that have been a major issue for treatment; hence, a leap towards naturally occurring immunomodulators was taken to develop safer methods of treatment. One of the major immune cells responsible for the growth of tumors is regulatory T cells (Tregs). To maintain immunological homeostasis, Treg dampens abnormal immune responses to self and non-self-antigens. The transcription factor FoxP3 is responsible for their lineage specification and takes part in the production of immunosuppressive cytokines like IL10, IL35, and TGFb. This helps cancer cells to proliferate without the restriction of different immune cells like CD8⁺T cells, dendritic cells, monocytes/macrophages, B cells, and natural killer cells. Hence, targeting Tregs to provide unhindered immunosurveillance has proven to be a breakthrough in cancer immunotherapy. This review mainly focuses on some common naturally occurring immunomodulators derived from plant products that have earned their place as immunotherapeutic agents, along with some of their ability to suppress Tregs that can be used as an effective way to treat cancer.