Recent Patents on Anti-Cancer Drug Discovery - Volume 14, Issue 1, 2019

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties. Objective: The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy. Methods: Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty. Results: TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability. Conclusion: The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.

Background: The immense development in the field of anticancer research has led to an increase in the research of bioactive compounds with anticancer potential. It has been known that many bioactive natural compounds have low solubility (and low bioavailability) as their main drawback when it comes to the formulation and drug delivery to specific sites. Objective: As many attempts have been made to overcome this issue, this review gives a summary of the current accomplishments regarding the development of new Drug Delivery Systems (DDSs) represented by nanoparticles (NPs) and exosomes. Methods: We analyzed the published data concerning selected compounds that present the most prominent plant secondary metabolites with anticancer potential, specifically flavone (quercetin), isoflavone (genistein and curcumin) and stilbene (resveratrol) groups that have been formulated as NPs and exosomes. In addition, we summarized the patent literature published from 2015-2018 that address these formulations. Results: Although the exact mechanism of action for the selected natural compounds still remains unclear, the anticancer effect is evident and the main research efforts are directed to finding the most suitable delivery systems. Recent patents in this field serve as evidence that these newly designed natural compound delivery systems could be powerful new anticancer agents in the very near future if the noted difficulties are overcome. Conclusion: The focus of recent research is not only to clarify the exact mechanisms of action and therapeutic effects, but also to answer the issue of suitable delivery systems that can transport sufficient doses of bioactive compounds to the desired target.

Background: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 Receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial. Objective: Current review was conducted to check involvement of P2X7R use in cancer treatment. Methods: We review the most recent patents focused on the use of P2X7R in the treatment of cancer. Results: P2X7R is an intriguing purinergic receptor that plays different roles in tumor progression. Conclusion: Powerful strategies able to selectively interfere with its expression and function should reveal helpful in the development of new anti-cancer therapies.

Background: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. Objective: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. Methods: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: “nicotine”, “nicotinic receptor”, and “addiction” or “COPD” or “lung cancer” were used. Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. Results: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. Conclusion: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.

Background: The most common solid malignancy of young men aged 20 to 34 years is testicular germ cell tumor. In addition, the incidence of these tumors has significantly increased throughout the last years. Testicular germ cell tumors are classified into seminoma and nonseminoma germ cell tumors, which take in yolk sac tumor, embryonal cell carcinoma, choriocarcinoma, and teratoma. There are noteworthy differences about therapy and prognosis of seminomas and nonseminoma germ cell tumors, even though both share characteristics of the primordial germ cells. Objectives: The study is focused on different molecular mechanisms strongly involved in testicular germ cell line tumors underlying new strategies to treat this human neoplasia. Methods: Bibliographic data from peer-reviewed research, patent and clinical trial literature, and around eighty papers and patents have been included in this review. Results: Our study reveals that several biomarkers are usefully utilized to discriminate among different histotypes. Moreover, we found new patents regarding testicular germ cell tumor treatments such as the expression of claudin 6, monoclonal antibody (Brentuximab Vedotin), immune checkpoint blockade (ICB) with the FDA-approved drugs pembrolizumab and nivolumab or the oncolytic virus Pelareorep, the combination of selective inhibitors of Aurora kinase. Conclusion: Finally, the pathogenesis of testicular germ cell tumor needs to be deeply understood so that it will improve data on stem cells, tumorigenesis and disease tumor management by more selective treatment.

Background: Chimeric Antigen Receptor (CAR) T cell immunotherapy, as an innovative method for tumor immunotherapy, acquires unprecedented clinical outcomes. Genetic modification not only provides T cells with the antigen-binding function but also endows T cells with better immunological functions both in solid and hematological cancer. However, the CAR T cell therapy is not perfect because of several reasons, such as tumor immune microenvironment, and autologous limiting factors of CAR T cells. Moreover, the safety of CAR T cells should be improved. Objective: Recently many patents and publications have reported the importance of CAR T cell immunotherapy. Based on the patents about CAR T cell immunotherapy, we conclude some methods for designing the CAR which can provide information to readers. Methods: In this review, we collect recent patents and publications, summarize some specific antigens for oncotherapy from patents and enumerate some approaches to conquering immunosuppression and reinforcing the immune response of CAR T cells. We also sum up some strategies for improving the safety of CAR T cell immunotherapy. Results: CAR T cell immunotherapy as a neotype cellular immunotherapy has been proved effective in oncotherapy and authorized by FDA. Improvements in CAR designing enhance functions of CAR T cells. Conclusion: This review, summarizing antigens and approaches to overcome defects of CAR T cell immunotherapy from patents and publications, might contribute to a broad readership.

Background: Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells. Objective: An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view. Methods: Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides. Results: The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets. Conclusion: These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.

Background: Cancer is one of the leading causes of death in the world and it is necessary to develop new strategies for its treatment because most therapies have limited access to many types of tumors, as well as low therapeutic efficacy and high toxicity. Objective: The present research aims to identify recent patents of drug delivery nanostructured systems that may have application in improving cancer treatment. Methods: Recent patents regarding the drug delivery nanostructured systems for cancer treatment were obtained from the patent databases of the six main patent offices of the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Intellectual Property Office of China and Korean Intellectual Property Office. Results: A total of 1710 patent documents from 1998 to 2017 including "drug delivery nanostructured systems for cancer treatment" were retrieved. The top five countries in patent share were USA, China, South Korea, Canada and Germany. The universities and enterprises of USA had the highest amount of patents followed by institutions from China. Conclusion: There is a strong tendency for the development of new nanostructured systems for the release of drugs; particularly, in recent years, the development of nanoparticles has focused on nanodiscs, gold nanoparticles and immunoliposomes.