Recent patents on anti-cancer drug discovery最新文献

Background: Enzalutamide has been approved clinically for the treatment of castrationresistant prostate cancer (CRPC) but is limited by the emergence of resistance. RhoA has been shown to play a vital role in carcinogenesis, invasion, and metastasis. However, the role of RhoA in enzalutamide-resistant prostate cancer (PCa) remains unclear.

Objectives: This study investigated the role of RhoA and the associated mechanisms of RhoA depletion in enzalutamide resistance in CRPC.

Methods: Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and colony formation assays were used to assess protein expression, survival, and proliferation of PCa cells, respectively. Xenograft experiments and hematoxylin and eosin (H&E) staining were used to detect further effects of RhoA on enzalutamide resistance in vivo.

Results: In the present study, the expression of RhoA, ROCK2, p38, p-p38, and AR was upregulated in enzalutamide-resistant PCa cells treated with enzalutamide, and silencing of RhoA or ROCK2 attenuated enzalutamide-resistant cell proliferation and colony formation. Furthermore, the deletion of RhoA dramatically increased the efficacy of enzalutamide in inhibiting 22RV1-derived xenograft tumor growth. Additionally, there was no significant change in ROCK1 expression in C4-2R cells treated with or without enzalutamide. Mechanistically, the knockdown of RhoA expression reverted the resistance to enzalutamide via RhoA/ROCK2/p38 rather than RhoA/ROCK1/p38.

Conclusion: Our results suggested that RhoA is a promising therapeutic target. As the inhibition of RhoA reverted enzalutamide resistance, it may increase its effectiveness in CRPC.

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.

Background: KRAS and BRAF targets are involved in the epidermal growth factor receptor pathway. KRAS and BRAF targets are the most frequent driver mutations in cancer.

Objective: The objective of the study was to present the recent developments in the KRAS target and the BRAF target.

Methods: KRAS target and BRAF target were analyzed by US patent analysis. All US granted patent documents from January 2002 to November 2021 were retrieved.

Results: The results showed both KRAS and BRAF targets to be attractive targets for developing anticancer drugs. The technology of RNA interference has been developed for drug discovery related to the KRAS target. Our study indicates that the structural screening of inhibitors between the KRAS target and the BRAF target should be an inverse option.

Conclusion: The chemical structures of inhibitors of BRAF target exhibited a unique classification of C07D405. The inhibitors of BRAF target could be used for the treatment of various cancers. However, the inhibitors of KRAS target did not show this feature. The present study provides new insight into drug discovery involving KRAS and BRAF targets.

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: 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.

Cancer is a leading cause of morbidity and mortality worldwide. Each year, millions of people worldwide are diagnosed with cancer, and more than half of them die. Various conventional therapies for cancer, including chemotherapy and radiotherapy, have extreme side effects. Therefore, to minimize the global burden of lethal diseases like cancer, an effective and novel drug must be discovered. Its patent should be acquired to secure the novel medicament. The pharmacological potential of different natural products has made them popular in the healthcare and pharmaceutical industries. Various anticancer compounds are obtained from natural sources such as plants, microbes, and marine and terrestrial animals, including alkaloids, terpenoids, biophenols, enzymes, glycosides, etc. The term "natural products" is defined as the product of secondary or non-essential metabolic processes produced by living organisms (such as plants, invertebrates, and microorganisms). Although more precise definitions of NPs exist, they do not always meet consensus. Others define NPs as small molecules (excluding biomolecules) that emerge from the metabolic reaction. A handful of effective compounds are used currently from natural or analog moieties, and many more are in clinical studies. There is an excellent need for patenting molecules from natural products as the hit lead molecules are derived, isolated, and synthesized from natural products. However, these naturally occurring products may not be patentable under the law because they come from nature. This review highlights why natural products and compounds are hard to patent, under what patent law criteria we can patent these natural products and compounds, patent procedural guideline sources and why researchers prefer publication rather than a patent. Here, various patent scenarios of natural products and compounds for cancer have been given.

Background: Cancer is a global health issue and economic burden with a continuous increase in incidence and mortality. Over the years, the underlying molecular mechanism of cancers was thoroughly researched, leading to multiple drugs' development. Unfortunately, most drugs have some serious drawbacks, such as therapy resistance and toxicity. Epidemiological studies have shown that a diet rich in fruits and vegetables has cancer prevention properties, which shifted the attention to the potential role of phytochemicals in anti-carcinogenic activity.

Objective: To review the present status of phytochemicals research and patents in cancer prevention and chemosensitization.

Methods: We explored the relevant published articles and patents to review the phytochemicals showing cancer preventive role in preclinical settings from 1997 onwards.

Results: We summarise the role of phytochemicals on anti-carcinogenic, anti-inflammatory, antiproliferative, anti-metastatic, and pro-apoptotic activities in both in vitro and in vivo. Thus, phytochemicals might be an excellent chemosensitizing agent against chemoresistant cells and possibly one of the safest and most effective options for cancer therapy. However, one of the limitations of phytochemicals is their poor bioavailability and rapid excretion. Several analogs have been introduced to increase bioavailability, better biological efficacy, absorption, and retention. In fact, various phytochemicals and their analogs have been patented for their anti-cancerous properties.

Conclusion: This mini-review discusses various phytochemicals and their anti-cancerous and chemosensitizing roles. Due to their clinical relevance, recent trends in phytochemical extraction and exploration have shown that more and more phytochemicals are being patented.

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.