Recent Patents on Anti-Cancer Drug Discovery - Volume 18, Issue 3, 2023

Background: Scientists, academicians, and researchers from academics and the pharmaceutical industries have all expressed interest in the design and production of pharmaceutical cocrystals in recent years. The development of novel drug products with enhanced physicochemical and pharmacological characteristics is aided by the cocrystallization of drug substances. Objective: The major problem with drug candidates is their solubility and bioavailability, which may be solved with the appropriate molecular modifications. The failure of most drug candidates in earlier clinical trials is also reawakening interest. In that connection, pharmaceutical cocrystals are vital in the development of dosage forms in the field of pharmaceutical technology. The goal of this manuscript is to provide a comprehensive overview of cocrystal synthesis methods and characterization techniques. Conclusion: In this review, it is evident that the solvent-free technique has several benefits over solvent-based approaches in the design and production of pharmaceutical cocrystals, and that these methodologies can also open opportunities for further advancement in the field of cocrystal synthesis. This manuscript provides a brief overview of each technique for manufacturing pharmaceutical cocrystals and an analysis of cocrystals. This manuscript has highlighted points on whether cocrystals comply with the requirements for intellectual property rights and how they will impact the current pharmaceutical industry. The impact of recent patents on pharmaceutical cocrystals is examined in depth with relevant examples.

Green nanotechnology can offer notable advantages over the conventional drug delivery methods in terms of improved drug stability, drug-carrying capacity, site-specificity, and feasibility to apply different routes of administration with less systemic toxicities. Metal nanoparticles bio fabricated with phytoconstituents and microbial extracts have gained significant interest for the treatment of various solid tumors including hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is an aggressive cancer with a very poor prognosis. The current treatments of HCC fails to provide tumor specificity, causing many systemic toxicities and poor overall survival benefits especially for patients in advanced and terminal stages. A novel therapeutic approach with maximal therapeutic effect and minimum adverse effects are urgently required for HCC patients. Green synthesized metal nanoparticles offer significant anticancer effects along with minimal systemic toxicities because of their site-specific delivery into the tumor microenvironment (TME). Green synthesized metal nanoparticles can therefore be a highly beneficial strategy for the treatment of HCC if properly validated with preclinical and clinical studies. This review focuses on the preclinical evidence of the most widely studied green metal nanoparticles such as green synthesized silver nanoparticles, gold nanoparticles and selenium nanoparticles. We have also summarised the clinical studies and the patents approved for nanoparticles against HCC.

Background: Nanotechnology plays a vital role in the field of medicine. Especially various nanoparticles such as silver, gold, platinum are involved in the treatment of different types of cancer. The effective nanoparticles were synthesized using techniques like chemical, physical, electrochemical and biological methods. In order to overcome the limitations existing in the synthesis of nanoparticles, researchers turned their attention toward the biological single step nanoparticle synthesis method by using plant and plant products. Objective: The objective of this study is to overcome the side effects encountered in the existing anti- cancer agents like nonspecificity and fast excretion, and plant-derived nanoparticles that are ecofriendly, cost-effective and biologically active could serve as a promising alternative. Conclusion: From the thorough literature review and recent patents, it is understood that the plantderived nanoparticles exhibited an excellent anti-proliferation anti-tumor activity towards different types of cancers without affecting the normal cells. Especially, the traditional chemotherapeutic drugs obtained from the plant source incorporated with the nanoparticles show remarkable results against anti cancer studies. The present review focused on some of the existing herbal plant derived nanoparticles, formulations and their potential application in cancer therapeutics.

Background: Gastrointestinal cancer are the major form of cancer in developing countries, which comprises gastric cancer (GC), hepatic cancer (HCC), colorectal cancers (CRC), etc.; they account for a large number of cancer-related deaths globally. Gastrointestinal cancers generally have a multifactorial origin, where both genetic and dietary factors play prominent roles. PI3K/Akt signaling is the prime signaling pathway associated with the Phosphoinositide-3 kinase/protein kinase B signaling pathway. Objectives: The present review aims to summarize the role of the PI3K/Akt signaling pathway on the different events of gastrointestinal cancers, such as proliferation, survival, metastasis, angiogenesis, drug resistance and stem cell properties. Methods: Literature collection has been done using the appropriate keywords from Pub- Med/Medline, Scopus, Web of science, or Eurekaselect. The details of individual types of cancers were selected by giving respective keywords. Results: PI3K signaling pathway is important in various gastrointestinal carcinogenesis and progression events; the pathway is involved in proliferation, survival, metastasis, and drug resistance. Several natural phytochemicals and their derivatives have been shown to inhibit PI3K signaling and its downstream regulatory elements, subsequently resulting in anticancer and anti-metastatic activity. Although numerous preclinical evidences are available, conclusive clinical reports are lacking on the anticancer aspects of PI3K inhibitors in gastric cancer. Conclusion: Phytochemicals are promising drug candidates for targeting the PI3K/mTOR pathway in various gastrointestinal cancer treatments. However, there is a need for extensive clinical studies to ascertain the commercial value of anticancer therapeutic compounds against cancers of the stomach, liver, and intestine.

Background: Chemotherapeutic drugs are principally intended to treat breast cancer. However, sooner or later, tumor drug resistance developed. These chemo drugs are effective but with numerous side effects. Breast cancer care may be extremely difficult since recurring cancer is frequently pre-treated with powerful agents. Cancer cells acquire high resistance to earlier therapies, necessitating alternative and more powerful drugs. Nanoparticles (NPs) as a medication delivery technology can overcome medication resistance in breast cancer and significantly reduce the effective dose. The off-targeted nature of chemo drugs can be resolved by encapsulating or attaching chemo drugs in nanocarriers, specifically targeting breast cancer cells. Objectives: This review highlights various chemo drugs for breast cancer and their encapsulation or bioconjugation with nanoparticles for its targeted delivery. Conclusion: Nanoparticles may subsist valuable abet in breast cancer management in this regard. Given that traditional chemotherapy approaches have been demonstrated to have several side effects and defects during treatment, the NPs-mediated drug delivery mechanism is a possible contender for replacement as a new technique.

Background: Cancer is characterized by uncontrolled cell division in the human body damaging normal tissues. There are almost a hundred types of cancers studied to date that are conventionally treated with chemotherapy, radiation therapy, and surgery. Conventional methods have drawbacks like non-specific distribution of drugs, low concentration of drugs in tumors, and adverse effects like cardiotoxicity. Therefore, inorganic nanoparticles are explored nowadays to achieve better results in cancer treatment. Objective: The objective of this review paper was to summarize the role of inorganic nanoparticles in cancer treatment by revealing their preclinical status and patents. Methods: Literature survey for the present work was conducted by exploring various search engines like PubMed, Google Scholar, and Google patents. Results: Inorganic nanoparticles come under the advanced category of nanomedicine explored in cancer therapeutics. The structural properties of inorganic nanoparticles make them excellent candidates for targeting, imaging, and eradication of cancer cells. Besides this, they also show high biocompatibility and minimum systemic toxicity. Conclusion: This review paper concludes that inorganic nanoparticles may be better alternatives to conventional approaches for the treatment of cancer. However, their presence in global pharmaceutical markets will be governed by the development of novel scale-up techniques and clinical evaluation.

Many cancer patients die due to their treatment failing because of their disease's resistance to chemotherapy and other forms of radiation therapy. Resistance may develop at any stage of therapy, even at the beginning. Several factors influence current therapy, including the type of cancer and the existence of genetic abnormalities. The response to treatment is not always predicted by the existence of a genetic mutation and might vary for various cancer subtypes. It is clear that cancer patients must be assigned a particular treatment or combination of drugs based on prediction models. Preliminary studies utilizing artificial intelligence-based prediction models have shown promising results. Building therapeutically useful models is still difficult despite enormous increases in computer capacity due to the lack of adequate clinically important pharmacogenomics data. Machine learning is the most widely used branch of artificial intelligence. Here, we review the current state in the area of using machine learning to predict treatment response. In addition, examples of machine learning algorithms being employed in clinical practice are offered.

Background: Colorectal cancer (CRC) is the third most widely spread tumor among the human population. It is usually adenocarcinomatous and develops as a polyp on the inner wall of the colon or rectum which may become malignant with time. Though its treatment is limited, its early diagnosis and prevention play a better role, thereby decreasing mortality rates. Objective: The molecular markers in CRC-affected tissues may play an important role to develop novel strategies to cure the disease. Nanotechnology consists of both an innovative diagnostic and therapeutic array of nanomaterials that may be used to target CRC like dendrimers, carbon nanotubes, nanoparticles, nano-emulsions, etc. Methods: Current patents and research covering the nanotechnology used to target and diagnose CRC is included in the review. Results: Nanotechnology is playing a wonderful role in both the treatment and diagnosis of CRC. Conclusion: The present review may cover the recent advancements in nanotechnology in the treatment and diagnosis of CRC.

Background: Gliotoxin, a secondary metabolite isolated from marine-derived Aspergillus fumigatus, has demonstrated anti-tumor properties in several cancers. Ferroptosis, a recently discovered type of programmed cell death that depends on the accumulation of iron and lipid peroxides, participates in the occurrence and development of various diseases, including cancer. A recent patent, US20200383943, has suggested that the promotion of ferroptosis is a method of cancer treatment. Therefore, the development of drugs that induce ferroptosis in cancer cells would constitute a novel therapeutic approach. Objective: Gliotoxin is a natural compound which has exhibited anti-tumor properties in multiple cancers, however, studies of the effect of gliotoxin on esophageal cancer are lacking. Although cancer treatment has shown great progress, including traditional surgery, chemotherapy, radiotherapy, and immunotherapy, the prognosis of esophageal cancer is still poor. Therefore, the development of new treatment approaches for esophageal cancer is necessary. Methods: The effects of gliotoxin on esophageal cancer cells were determined by functional assays, such as CCK-8, wound healing and transwell assays. We used online tools to predict the target genes of gliotoxin, followed by further verification using Western blotting assays. To assess the role of gliotxin in inducing ferroptosis in esophageal cancer, we detected characteristics associated with ferroptosis including ROS, MDA, GSH and Fe²⁺. Results: Using online tools SEA and SwissTargetPrediction, we predicted that SUV39H1 was the gliotoxin target gene. Furthermore, in esophageal cancer tissues, SUV39H1 was expressed at higher levels than in normal tissues, while in patients with Esophageal Squamous Cell Carcinoma (ESCC), high expression levels of SUV39H1 indicated a poor prognosis. In vitro, we observed that gliotoxin increased ESCC cell death and inhibited cell migration. We treated ESCC cells with pan-caspase inhibitor Z-VAD-FMK or ferroptosis inhibitors, including Fer-1 and DFO. Our results showed that Fer-1 and DFO reduced the toxic effects of gliotoxin, while Z-VAD-FMK did not. Furthermore, gliotoxin treatment reduced tumor weight and volume in the xenograft tumor mouse model. Conclusion: In summary, our findings indicate that gliotoxin downregulated SUV39H1 expression in ESCC cells and induced ferroptosis, suggesting a novel natural therapy for ESSC.

Objective: The objective of this study is to explore the potential anti-liver cancer mechanism of Huachansu injection through integrated bioinformatics analysis. Methods: Active ingredients of Huachansu injection (extraction of toad skin) were obtained, and their potential drug targets were predicted via SwissTargetPrediction database. Liver cancer disease targets were identified from the GEO (Gene Expression Omnibus) dataset and four public databases. Then Protein-Protein Interaction (PPI) network of toad skin was constructed. GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed subsequently. Finally, molecular docking was performed using Auto Dock Vina. Results: In the search for therapeutic targets, twenty active components of toad skin were screened for further study, five hundred and sixty-eight targets of components were identified. In the search for disease targets, three thousand two hundred and twenty-seven genes were identified after removal of duplicated genes, one hundred and fifty-nine genes were up-regulated in liver cancer samples while two hundred and seventy-eight were down-regulated in liver cancer patients. After predicting the therapeutic targets of the components, the results were cross-checked with the disease targets, thirteen up-regulated targets and ten down-regulated targets were obtained. Finally, in the results of molecular docking, seven targets (CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK) were potential up-regulated targets, three targets (SHBG, SRD5A2, NR1I2) were potential down-regulated targets, all of which have the best binding energy and molecular interactions. Conclusion: CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, and TTK could be potential upregulated target proteins of Huachansu injection for treating liver cancer. The mechanism of Huachansu injection in the treatment of liver cancer through these up-regulated targets is related to cell cycle, cellular senescence, viral carcinogenesis, p53 signaling pathway. SHBG, SRD5A2, and NR1I2 could be potential down-regulated target proteins of Huachansu injection in treating liver cancer.;