-
Pharmacology & Therapeutics May 2024Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug... (Review)
Review
Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug discovery, but there is growing recognition of the importance of the more complex orthotopic and metastatic tumour models for understanding both target biology in the correct tissue context, and the impact of the tumour microenvironment and the immune system in responses to treatment. The aim of this review is to highlight the value that orthotopic and metastatic models bring to the study of tumour biology and drug development while pointing out those models that are most likely to be encountered in the literature. Important developments in orthotopic models, such as the increasing use of early passage patient material (PDXs, organoids) and humanised mouse models are discussed, as these approaches have the potential to increase the predictive value of preclinical studies, and ultimately improve the success rate of anticancer drugs in clinical trials.
Topics: Animals; Mice; Humans; Xenograft Model Antitumor Assays; Immune System; Antineoplastic Agents; Neoplasms; Disease Models, Animal; Tumor Microenvironment
PubMed: 38467308
DOI: 10.1016/j.pharmthera.2024.108631 -
Biomedicine & Pharmacotherapy =... Oct 2022The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and... (Review)
Review
The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-β), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving the physicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Inflammation; Nanomedicine; Neoplasms; Polyesters; Signal Transduction
PubMed: 36067568
DOI: 10.1016/j.biopha.2022.113654 -
International Journal of Molecular... Jul 2023Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited... (Review)
Review
Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited translational significance, animal ethics, and inter-species physiological differences. In this regard, 3D cellular models can be presented as a step forward in biomedical research, allowing for mimicking tissue complexity more accurately than traditional 2D models, while also contributing to reducing the use of animal models. In cancer research, 3D models have the potential to replicate the tumor microenvironment, which is a key modulator of cancer cell behavior and drug response. These features make cancer 3D models prime tools for the preclinical study of anti-tumoral drugs, especially considering that there is still a need to develop effective anti-cancer drugs with high selectivity, minimal toxicity, and reduced side effects. Metallodrugs, especially transition-metal-based complexes, have been extensively studied for their therapeutic potential in cancer therapy due to their distinctive properties; however, despite the benefits of 3D models, their application in metallodrug testing is currently limited. Thus, this article reviews some of the most common types of 3D models in cancer research, as well as the application of 3D models in metallodrug preclinical studies.
Topics: Animals; Neoplasms; Antineoplastic Agents; Tumor Microenvironment; Models, Animal; Drug Development
PubMed: 37569291
DOI: 10.3390/ijms241511915 -
European Journal of Pharmacology Sep 2020Oncological diseases are invariably a challenge for the modern world. Therefore, in recent decades, scientists have begun to look for compounds of natural origin that... (Review)
Review
Oncological diseases are invariably a challenge for the modern world. Therefore, in recent decades, scientists have begun to look for compounds of natural origin that will be able to support or independently be used in oncological therapy. Among the antimicrobial proteins (AMPs), a promising family of peptides isolated from the immunized hemolymph of Hyalophora cecropia pupae has been distinguished. The cecropin family is not only characterized by antimicrobial and antifungal properties, but most importantly also has anticancer properties. Their antitumor potential is confirmed by in vitro studies conducted on several different cell lines, among others, prostate and breast cancer cell lines. This paper presents publications demonstrating cytolytic properties against tumour cells of members belonging to the cecropin family, as well as synthesized cecropin B with the introduced modification of its sequence and conjugated cecropin B with a modified luteinizing hormone-releasing hormone (LHRH). Moreover, three models of cecropin mechanisms of action are also described. The benefits and limitations associated with the use of these peptides in oncological therapy have also been demonstrated.
Topics: Animals; Antineoplastic Agents; Cecropins; Humans; Neoplasms
PubMed: 32603694
DOI: 10.1016/j.ejphar.2020.173317 -
Molecules (Basel, Switzerland) Jul 2022Cyclic peptides have been widely reported to have therapeutic abilities in the treatment of cancer. This has been proven through in vitro and in vivo studies against... (Review)
Review
Cyclic peptides have been widely reported to have therapeutic abilities in the treatment of cancer. This has been proven through in vitro and in vivo studies against breast, lung, liver, colon, and prostate cancers, among others. The multitude of data available in the literature supports the potential of cyclic peptides as anticancer agents. This review summarizes the findings from previously reported studies and discusses the different cyclic peptide compounds, the sources, and their modes of action as anticancer agents. The prospects and future of cyclic peptides will also be described to give an overview on the direction of cyclic peptide development for clinical applications.
Topics: Antineoplastic Agents; Humans; Neoplasms; Peptides; Peptides, Cyclic
PubMed: 35889301
DOI: 10.3390/molecules27144428 -
Molecules (Basel, Switzerland) Sep 2023Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as... (Review)
Review
Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as multidrug resistance, poor specificity, selectivity, and toxicity. The aforementioned factors contribute to treatment failure. Hybrid compounds have features that can overcome the limitations mentioned above. Chlorambucil, an anticancer drug that is used to treat prostate and breast cancer, suffers from poor aqueous solubility and specificity, a short half-life, and severe side effects, including anaemia and bone marrow suppression. It compromises the immune system, resulting in treatment failure. Hence, its combination with other pharmacophores has been reported to result in effective anticancer agents with fewer side effects and high therapeutic outcomes. Furthermore, this review gives an update (2010 to date) on the developments of chlorambucil hybrid compounds with anticancer activity, and the structure-activity relationship (SAR), and also highlights future strategies for developing novel anticancer agents.
Topics: Male; Humans; Chlorambucil; Antineoplastic Agents; Structure-Activity Relationship; Breast Neoplasms; Pharmacophore
PubMed: 37836732
DOI: 10.3390/molecules28196889 -
International Journal of Molecular... Feb 2022DNA damage response (DDR) is critical to ensure genome stability, and defects in this signaling pathway are highly associated with carcinogenesis and tumor progression.... (Review)
Review
DNA damage response (DDR) is critical to ensure genome stability, and defects in this signaling pathway are highly associated with carcinogenesis and tumor progression. Nevertheless, this also provides therapeutic opportunities, as cells with defective DDR signaling are directed to rely on compensatory survival pathways, and these vulnerabilities have been exploited for anticancer treatments. Following the impressive success of PARP inhibitors in the treatment of -mutated breast and ovarian cancers, extensive research has been conducted toward the development of pharmacologic inhibitors of the key components of the DDR signaling pathway. In this review, we discuss the key elements of the DDR pathway and how these molecular components may serve as anticancer treatment targets. We also summarize the recent promising developments in the field of DDR pathway inhibitors, focusing on novel agents beyond PARP inhibitors. Furthermore, we discuss biomarker studies to identify target patients expected to derive maximal clinical benefits as well as combination strategies with other classes of anticancer agents to synergize and optimize the clinical benefits.
Topics: Animals; Antineoplastic Agents; DNA Repair; Humans; Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Signal Transduction
PubMed: 35163621
DOI: 10.3390/ijms23031701 -
International Journal of Molecular... May 2023Precision oncology, also known as personalized medicine, is an evolving approach to cancer treatment that aims to tailor therapies to individual patients based on their...
Precision oncology, also known as personalized medicine, is an evolving approach to cancer treatment that aims to tailor therapies to individual patients based on their unique molecular profile, including genetic alterations and other biomarkers [...].
Topics: Humans; Neoplasms; Precision Medicine; Antineoplastic Agents; Biomarkers; Medical Oncology; Biomarkers, Tumor
PubMed: 37175963
DOI: 10.3390/ijms24098259 -
International Journal of Molecular... Jun 2022With advances in cancer-targeting therapeutic strategies, cancer cells have developed drug resistance [...].
With advances in cancer-targeting therapeutic strategies, cancer cells have developed drug resistance [...].
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 35742888
DOI: 10.3390/ijms23126445 -
Cells Aug 2019Combination chemotherapy has been a mainstay in cancer treatment for the last 60 years. Although the mechanisms of action and signaling pathways affected by most... (Review)
Review
Combination chemotherapy has been a mainstay in cancer treatment for the last 60 years. Although the mechanisms of action and signaling pathways affected by most treatments with single antineoplastic agents might be relatively well understood, most combinations remain poorly understood. This review presents the most common alterations of signaling pathways in response to cytotoxic and targeted anticancer drug treatments, with a discussion of how the knowledge of signaling pathways might support and orient the development of innovative strategies for anticancer combination therapy. The ultimate goal is to highlight possible strategies of chemotherapy combinations based on the signaling pathways associated with the resistance mechanisms against anticancer drugs to maximize the selective induction of cancer cell death. We consider this review an extensive compilation of updated known information on chemotherapy resistance mechanisms to promote new combination therapies to be to discussed and tested.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Humans; Neoplasms; Signal Transduction
PubMed: 31480389
DOI: 10.3390/cells8091013