{"title":"Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology","authors":"Ruby Srivastava","doi":"10.5772/intechopen.102343","DOIUrl":"https://doi.org/10.5772/intechopen.102343","url":null,"abstract":"Activated Cdc42-associated kinase 1 (ACK1) is an intracellular non-receptor tyrosine kinase referred to as TNK2, which is considered as an oncogene and therapeutic target in various cancers including breast cancer, non-small-cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and many others. Oncogenic non-receptor tyrosine kinase mutations occur either due to point mutations, duplications or insertions and deletions, or by involving in the development of a fusion gene resulting from a chromosomal rearrangement. ACK1 is involved with multiple signaling pathways of tumor progression. With these signaling networks, ACK1 participates in cell survival, invasion, migration, and tumorigenesis that are strongly related to the prognosis and clinicopathology of cancers. Previous studies predicted that ACK1 is a carcinogenic factor and blockage of ACK1 inhibits cancer cell survival, proliferation, migration, and radiation resistance. FDA has approved many multi-kinase inhibitors as therapeutic drugs that show good inhibitory activity not against ACK1 but also towards multiple targets. As ACK1 is a key target for other neurological diseases, inflammation, and immunological diseases also, so the studies on these inhibitors not only provide potential strategies for the treatment of cancers that require simultaneous targeting of multiple targets but also can be used in drug repurposing for other diseases.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132381887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonaid Ahmad Malik, Rafia Jan, S. Ahmed, Sirajudheen Anwar
{"title":"Breast Cancer Drug Repurposing a Tool for a Challenging Disease","authors":"Jonaid Ahmad Malik, Rafia Jan, S. Ahmed, Sirajudheen Anwar","doi":"10.5772/intechopen.101378","DOIUrl":"https://doi.org/10.5772/intechopen.101378","url":null,"abstract":"Drug repurposing is one of the best strategy for drug discovery. There are several examples where drug repurposing has revolutionized the drug development process, such as metformin developed for diabetes and is now employed in polycystic ovarian syndrome. Drug repurposing against breast cancer is currently a hot topic to look upon. With the continued rise in breast cancer cases, there is a dire need for new therapies that can tackle it in a better way. There is a rise of resistance to current therapies, so drug repurposing might produce some lead candidates that may be promising to treat breast cancer. We will highlight the breast cancer molecular targets, currently available drugs, problems with current therapy, and some examples that might be promising to treat it.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125244654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ran Zhang, R. Oerlemans, Chao Wang, Lili Zhang, Matthew R. Groves
{"title":"Drug Repurposing Techniques in Viral Diseases","authors":"Ran Zhang, R. Oerlemans, Chao Wang, Lili Zhang, Matthew R. Groves","doi":"10.5772/intechopen.101443","DOIUrl":"https://doi.org/10.5772/intechopen.101443","url":null,"abstract":"Since the advent of the twentieth century, several severe virus outbreaks have occurred—H1N1 (1918), H2N2 (1957), H3N2 (1968), H1N1 (2009) and recently COVID-19 (2019)—all of which have posed serious challenges to public health. Therefore, rapid identification of efficacious antiviral medications is of ongoing paramount importance in combating such outbreaks. Due to the long cycle of drug development, not only in the development of a “safe” medication but also in mandated and extensive (pre)clinical trials before a drug can be safely licensed for use, it is difficult to access effective and safe novel antivirals. This is of particular importance in addressing infectious disease in appropriately short period of time to limit stress to ever more interlinked societal infrastructures; including interruptions to economic activity, supply routes as well as the immediate impact on health care. Screening approved drugs or drug candidates for antiviral activity to address emergent diseases (i.e. repurposing) provides an elegant and effective strategy to circumvent this problem. As such treatments (in the main) have already received approval for their use in humans, many of their limitations and contraindications are well known, although efficacy against new diseases must be shown in appropriate laboratory trials and clinical studies. A clear in this approach in the case of antivirals is the “relative” simplicity and a high degree of conservation of the molecular mechanisms that support viral replication—which improves the chances for a functional antiviral to inhibit replication in a related viral species. However, recent experiences have shown that while repurposing has the potential to identify such cases, great care must be taken to ensure a rigourous scientific underpinning for repurposing proposals. Here, we present a brief explanation of drug repurposing and its approaches, followed by an overview of recent viral outbreaks and associated drug development. We show how drug repurposing and combination approaches have been used in viral infectious diseases, highlighting successful cases. Special emphasis has been placed on the recent COVID-19 outbreak, and its molecular mechanisms and the role repurposing can/has play(ed) in the discovery of a treatment.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131134735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Repurposing Market Drugs to Target Epigenetic Enzymes in Human Diseases","authors":"Aishat Motolani, Mat Martin, Steven Sun, T. Lu","doi":"10.5772/intechopen.101397","DOIUrl":"https://doi.org/10.5772/intechopen.101397","url":null,"abstract":"Drug discovery is an exciting yet highly costly endeavor. In the United States, developing a new prescription medicine that gains marketing approval takes near a decade and costs drugmakers for near 3 billion. More challengingly, the success rate of a compound entering phase I trials is just slightly under 10%. Because of these mounting hurdles, repurposing market approved drugs to new clinical indications has been a new trend on the rise. Another merit to this approach is the already confirmed toxicity profiles of the drugs and their possession of drug-like features. Thus, repurposed drugs can reach the market approved stage in a much faster, cheaper, and more efficient way. Notably, epigenetic enzymes play a critical role in the etiology and progression of different diseases. Researchers are now assessing the possibilities of using market approved drugs to target epigenetic enzymes as a novel strategy to curtail disease progression. Thus, in this book chapter, we will provide an outlook on repurposing market drugs to target epigenetic enzymes in various diseases. Consequently, this book chapter will not only provide the readers with current knowledge in this specific field, but also will shed light on the pathway forward for repurposing market drugs to target epigenetic enzymes in human diseases.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123606020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhilong Jia, Xinyu Song, Jinlong Shi, Wei-dong Wang, K. He
{"title":"Gene Signature-Based Drug Repositioning","authors":"Zhilong Jia, Xinyu Song, Jinlong Shi, Wei-dong Wang, K. He","doi":"10.5772/intechopen.101377","DOIUrl":"https://doi.org/10.5772/intechopen.101377","url":null,"abstract":"With the advent of dynamical omics technology, especially the transcriptome and proteome, a huge amount of data related to various diseases and approved drugs are available under multi global projects or researches with their interests. These omics data and new machine learning technology largely promote the translation of drug research into clinical trials. We will cover the following topics in this chapter. 1) An introduction to the basic discipline of gene signature-based drug repurposing; 2) databases of genes, drugs and diseases; 3) gene signature databases of the approved drugs; 4) gene signature databases of various diseases; 5) gene signature-based methods and tools for drug repositioning; 6) new omics technology for drug repositioning; 7) drug repositioning examples with reproducible code. And finally, discuss the future trends and conclude.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"85 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126285651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast Cancer: A Review","authors":"Panneerselvam Theivendren, Selvaraj Kunjiappan, Yashoda Mariappa Hegde, Kaveena Ravi, Sivakumar Vellaichamy, M. Gopal, Manimekalai Pichaivel","doi":"10.5772/intechopen.100143","DOIUrl":"https://doi.org/10.5772/intechopen.100143","url":null,"abstract":"Breast cancer is a major health concern as it is the second leading cause of death from cancer. There are several well-known risk factors that contribute to breast cancer. Despite the various treatment options available, complete cure is still difficult due to heterogenicity of BC subtypes. As a result, identifying BC subtypes is critical for determining the optimal treatment approach. Over the last several years, new drugs targeting particular therapeutic targets have resulted in significant advances in the treatment of breast cancer. Nonetheless, resistance to treatment is the “major” issue, and a significant increase in survival rates has been the main focus for researchers. The purpose of this review article is to provide a broad overview of the molecular basis of drug resistance in breast cancer, as well as a detailed assessment of current treatment options, potential new treatment methods for drug-resistant breast cancer and repurposed drugs used for treatment. The possibility of non-cancer drugs being studied for breast cancer in the future, as well as the obstacles and bottlenecks of drug repurposing, is also highlighted. Finally, we go through present problems and future prospects in drug-resistant breast cancer therapy.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131910190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hina Qayoom, Umar Mehraj, Shariqa Aisha, Shazia Sofi, M. A. Mir
{"title":"Integrating Immunotherapy with Chemotherapy: A New Approach to Drug Repurposing","authors":"Hina Qayoom, Umar Mehraj, Shariqa Aisha, Shazia Sofi, M. A. Mir","doi":"10.5772/intechopen.100183","DOIUrl":"https://doi.org/10.5772/intechopen.100183","url":null,"abstract":"Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking the three hormonal receptors namely estrogen receptor, progesterone receptor and HER2 receptor, and the only treatment option available for TNBC is chemotherapy. Chemotherapy lacks specificity since it acts on normal healthy cells as well resulting into secondary diseases in TNBC patients. In addition chemotherapy poses recurrence and relapse issues due to the development of chemoresistance among TNBC patients. Immunotherapy remarkably immune checkpoint inhibitors show a great therapeutic potential in TNBC. As TNBC contain an increased TILs (tumor infiltrating lymphocytes) infiltration making it more suitable as a therapeutic target anti-tumor immune strategy. Moreover, evidences have indicated that chemotherapy upregulates the anti-tumor immune response in TNBC. As a result, a combination of immunotherapy with chemotherapy may increase the overall relapse and recurrence free survival of TNBC patients. Therefore, in this chapter we will focus on how the immunotherapy works in TNBC, their effects and consequences. We will further be discussing the clinical studies and the importance of immune checkpoint inhibitors (ICIs) in combination with various therapeutic agents and target. Further, we will explore the processes involved.","PeriodicalId":186653,"journal":{"name":"Drug Repurposing - Molecular Aspects and Therapeutic Applications [Working Title]","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130243240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}