Gabrielle Brewer, Anne-Marie Fortier, Morag Park, Christopher Moraes
Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.
{"title":"The case for cancer-associated fibroblasts: essential elements in cancer drug discovery?","authors":"Gabrielle Brewer, Anne-Marie Fortier, Morag Park, Christopher Moraes","doi":"10.4155/fdd-2021-0004","DOIUrl":"https://doi.org/10.4155/fdd-2021-0004","url":null,"abstract":"<p><p>Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.</p>","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/c6/fdd-04-71.PMC9112234.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eswara Naga Hanuma Kumar Ghali, Vijian Dhevan, Shravan K Narmala, Meena Jaggi, Subhash C Chauhan, Murali M Yallapu
Eswara Naga Hanuma Kumar Ghali1,2, Vijian Dhevan3, Shravan K Narmala4, Meena Jaggi1,2, Subhash C Chauhan1,2 & Murali M Yallapu*,1,2 1Department of Immunology & Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA 2South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA 3Department of Surgery, University of Texas Rio Grande Valley, Harlingen, TX 78550, USA 4DHR Health Hematology Oncology Institute, DHR Health, Edinburg, TX 78539, USA *Author for correspondence: Tel.: +956 296 1734; murali.yallapu@utrgv.edu
{"title":"Breakthrough medicines during the COVID-19 pandemic era.","authors":"Eswara Naga Hanuma Kumar Ghali, Vijian Dhevan, Shravan K Narmala, Meena Jaggi, Subhash C Chauhan, Murali M Yallapu","doi":"10.4155/fdd-2022-0002","DOIUrl":"https://doi.org/10.4155/fdd-2022-0002","url":null,"abstract":"Eswara Naga Hanuma Kumar Ghali1,2, Vijian Dhevan3, Shravan K Narmala4, Meena Jaggi1,2, Subhash C Chauhan1,2 & Murali M Yallapu*,1,2 1Department of Immunology & Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA 2South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA 3Department of Surgery, University of Texas Rio Grande Valley, Harlingen, TX 78550, USA 4DHR Health Hematology Oncology Institute, DHR Health, Edinburg, TX 78539, USA *Author for correspondence: Tel.: +956 296 1734; murali.yallapu@utrgv.edu","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/4b/fdd-04-69.PMC8842712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9730310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinetic intracellular assay measures compound binding kinetics at intracellular targets within living cells","authors":"Charles S Lay, Daniel A. Thomas, P. Craggs","doi":"10.4155/fdd-2021-0010","DOIUrl":"https://doi.org/10.4155/fdd-2021-0010","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43935920","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}
A. Banegas-Luna, Miguel Carmena-Bargueño, H. Pérez‐Sánchez
{"title":"Quo vadis artificial intelligence and personalized medicine?","authors":"A. Banegas-Luna, Miguel Carmena-Bargueño, H. Pérez‐Sánchez","doi":"10.4155/fdd-2021-0009","DOIUrl":"https://doi.org/10.4155/fdd-2021-0009","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44664356","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}
Carlton Bijesh Ray, Vinesan Vijayarasa, Maariyah Vankad, M. Sherif, A. Harky
Lung cancers have the worst incident and mortality rates. Cancers such as advanced non-small-cell lung carcinomas are inoperable and often the only treatment available is chemo-radiotherapy. There has been little improvement in long-term survival recently, prompting research into novel treatments. Immune checkpoint inhibitors (ICIs) are a form of immunotherapy used in lung cancer. The efficacy of ICIs is dependent on: the part of the pathway affected; the presence of prognostic biomarkers; the method of efficacy assessment; the stage of the disease and other drugs involved. Monoclonal antibodies, Toll-like receptor agonists and cancer vaccines have shown modest effects on survival. Refinement of treatment regimens and prognostic biomarkers will help improve the survival of patients in the future.
{"title":"The role of immunotherapy in treating lung cancer: current status and future perspective","authors":"Carlton Bijesh Ray, Vinesan Vijayarasa, Maariyah Vankad, M. Sherif, A. Harky","doi":"10.4155/fdd-2021-0006","DOIUrl":"https://doi.org/10.4155/fdd-2021-0006","url":null,"abstract":"Lung cancers have the worst incident and mortality rates. Cancers such as advanced non-small-cell lung carcinomas are inoperable and often the only treatment available is chemo-radiotherapy. There has been little improvement in long-term survival recently, prompting research into novel treatments. Immune checkpoint inhibitors (ICIs) are a form of immunotherapy used in lung cancer. The efficacy of ICIs is dependent on: the part of the pathway affected; the presence of prognostic biomarkers; the method of efficacy assessment; the stage of the disease and other drugs involved. Monoclonal antibodies, Toll-like receptor agonists and cancer vaccines have shown modest effects on survival. Refinement of treatment regimens and prognostic biomarkers will help improve the survival of patients in the future.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48970587","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}
S. Bonam, M. Sekar, Girija S Guntuku, S. G. Nerella, Krishna M Pawar A, S. Challa, Gopala Kmt Eswara, Sivamma Mettu
The recent emergence of COVID-19 influenced the layman’s knowledge of drugs. Although several drugs have been discovered serendipitously, research has moved to the next-generation era of drug discovery. The use of drugs is inevitable and they have become lifesavers in the present era. Although research from different scientific backgrounds has supported the translational research of drug discovery, the prime role of pharmacy has to be remembered. Here we have summarized the role of some important subjects in pharmacy education, which have paved different ways in drug discovery and development.
{"title":"Role of pharmaceutical sciences in future drug discovery","authors":"S. Bonam, M. Sekar, Girija S Guntuku, S. G. Nerella, Krishna M Pawar A, S. Challa, Gopala Kmt Eswara, Sivamma Mettu","doi":"10.4155/fdd-2021-0005","DOIUrl":"https://doi.org/10.4155/fdd-2021-0005","url":null,"abstract":"The recent emergence of COVID-19 influenced the layman’s knowledge of drugs. Although several drugs have been discovered serendipitously, research has moved to the next-generation era of drug discovery. The use of drugs is inevitable and they have become lifesavers in the present era. Although research from different scientific backgrounds has supported the translational research of drug discovery, the prime role of pharmacy has to be remembered. Here we have summarized the role of some important subjects in pharmacy education, which have paved different ways in drug discovery and development.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47969352","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}
Bioengineered in vitro models have advanced from 2D cultures and simple 3D cell aggregates to more complex organoids and organ-on-a-chip platforms. This shift has been substantial in cancer research; while simple systems remain in use, multi-tissue type tumor and tissue chips and patient-derived tumor organoids have grown rapidly. These more advanced models offer new tools to cancer researchers based on human tumor physiology and the potential for interactions with nontumor tissue physiology while avoiding critical differences between human and animal biology. In this focused review, the authors discuss the importance of organoid and organ-on-a-chip platforms, with a particular focus on modeling cancer, to highlight oncology-focused in vitro model platform technologies that improve upon the simple 2D cultures and 3D spheroid models of the past.
{"title":"Biofabrication of advanced in vitro and ex vivo cancer models for disease modeling and drug screening","authors":"Kylie G. Nairon, A. Skardal","doi":"10.4155/fdd-2020-0034","DOIUrl":"https://doi.org/10.4155/fdd-2020-0034","url":null,"abstract":"Bioengineered in vitro models have advanced from 2D cultures and simple 3D cell aggregates to more complex organoids and organ-on-a-chip platforms. This shift has been substantial in cancer research; while simple systems remain in use, multi-tissue type tumor and tissue chips and patient-derived tumor organoids have grown rapidly. These more advanced models offer new tools to cancer researchers based on human tumor physiology and the potential for interactions with nontumor tissue physiology while avoiding critical differences between human and animal biology. In this focused review, the authors discuss the importance of organoid and organ-on-a-chip platforms, with a particular focus on modeling cancer, to highlight oncology-focused in vitro model platform technologies that improve upon the simple 2D cultures and 3D spheroid models of the past.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45983601","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":"An interview with Dr. Mike Robertson on the development of novel drugs for HIV treatment in diverse populations","authors":"Michael Robertson","doi":"10.4155/fdd-2021-0007","DOIUrl":"https://doi.org/10.4155/fdd-2021-0007","url":null,"abstract":"","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47179990","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}
Tweetable abstract Reflections on challenges and promises of COVID-19 vaccine development show opportunities for innovation and collaboration between stakeholders.
对COVID-19疫苗开发挑战和前景的反思显示了利益攸关方之间的创新和合作机会。
{"title":"COVID-19 vaccines: challenges and promises of trials, manufacturing and allocation of doses","authors":"B. Spadaro","doi":"10.4155/fdd-2020-0031","DOIUrl":"https://doi.org/10.4155/fdd-2020-0031","url":null,"abstract":"Tweetable abstract Reflections on challenges and promises of COVID-19 vaccine development show opportunities for innovation and collaboration between stakeholders.","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44590936","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}
COVID-19 – the infectious disease caused by the SARS-CoV-2 virus, a member of the ssRNA coronavirus family – has given rise to over 51.5 million confirmed infections and 1,275,979 deaths worldwide, as of 12 November 2020 [1]. It is known to be related to both the SARS-CoV and MERS-CoV viruses, responsible for severe acute respiratory syndrome and Middle East respiratory syndrome, respectively [2–4]. Human-to-human transmission of COVID-19 is widely recognized to be through a respiratory mechanism [3]. The severity of the disease ranges from asymptomatic to fatal [4,5]. The main reported symptoms include fever, nonproductive cough and loss of taste and smell, with severe cases reporting acute respiratory distress, viral pneumonia and requiring intubation and mechanical ventilation [1,4,6]. To date, there is no clinically approved vaccine available, nor any antiviral drug treatment for severe cases of this disease [1,4]. Virus-encoded anti-infective targets A number of potential drug targets expressed by members of the coronavirus family have been identified. These include the ‘Spike’ glycoprotein, a trimer that binds to ACE2 on the host cell membrane [3,4]. This allows fusion of the viral and host cell membranes and viral entry into the cell [3]. Other potential targets include the cysteine proteases – 3CLpro (also known as Mpro) and PLpro – which are essential for production of new mature virions [7,8]. Another potential target is RdRP, which is needed for replication of the viral genome [5]. Drug repurposing In order to rapidly progress new drug therapies into clinical use against COVID-19, drug repurposing has been widely investigated [9]. This has the advantage that potential therapeutics have already been approved for use in humans [9]. Virtual screening has been widely employed to aid in the repurposing of existing drug therapies for COVID-19 [2,10]. This approach is more rapid and economical than conventional lab-based testing. A number of potential drug treatments have been identified using this process. These include remdesivir, previously used for treatment of the Ebola and hepatitis C viruses and ribavirin, previously used for treatment of respiratory syncytial virus infection, hepatitis C and some hemorrhagic fevers. Remdesivir is reported to target RdRP, whereas ribavirin has been reported to target both 3CLpro and RdRP [2,6,11]. Recently, the US FDA (MD, USA) approved the use of remdesivir for COVID-19 patients aged over 12 years [12]. However, the WHO (Geneva, Switzerland) have released unpublished data from a clinical trial suggesting remdesivir does not reduce the mortality rate, shorten hospital stays or reduce the need for ventilation in patients with severe COVID-19 [1]. Other clinical trials of drug combinations are still ongoing. Development of new therapeutic antiviral agents The need to develop novel, targeted antivirals to treat SARS-CoV-2 infection is clear. However, the drug discovery and development process is lik
{"title":"Evaluation of potential anti-COVID-19 therapies","authors":"Clare L Box, Kevin S J Thompson","doi":"10.4155/fdd-2020-0029","DOIUrl":"https://doi.org/10.4155/fdd-2020-0029","url":null,"abstract":"COVID-19 – the infectious disease caused by the SARS-CoV-2 virus, a member of the ssRNA coronavirus family – has given rise to over 51.5 million confirmed infections and 1,275,979 deaths worldwide, as of 12 November 2020 [1]. It is known to be related to both the SARS-CoV and MERS-CoV viruses, responsible for severe acute respiratory syndrome and Middle East respiratory syndrome, respectively [2–4]. Human-to-human transmission of COVID-19 is widely recognized to be through a respiratory mechanism [3]. The severity of the disease ranges from asymptomatic to fatal [4,5]. The main reported symptoms include fever, nonproductive cough and loss of taste and smell, with severe cases reporting acute respiratory distress, viral pneumonia and requiring intubation and mechanical ventilation [1,4,6]. To date, there is no clinically approved vaccine available, nor any antiviral drug treatment for severe cases of this disease [1,4].\u0000 Virus-encoded anti-infective targets\u0000 A number of potential drug targets expressed by members of the coronavirus family have been identified. These include the ‘Spike’ glycoprotein, a trimer that binds to ACE2 on the host cell membrane [3,4]. This allows fusion of the viral and host cell membranes and viral entry into the cell [3]. Other potential targets include the cysteine proteases – 3CLpro (also known as Mpro) and PLpro – which are essential for production of new mature virions [7,8]. Another potential target is RdRP, which is needed for replication of the viral genome [5].\u0000 Drug repurposing\u0000 In order to rapidly progress new drug therapies into clinical use against COVID-19, drug repurposing has been widely investigated [9]. This has the advantage that potential therapeutics have already been approved for use in humans [9]. Virtual screening has been widely employed to aid in the repurposing of existing drug therapies for COVID-19 [2,10]. This approach is more rapid and economical than conventional lab-based testing. A number of potential drug treatments have been identified using this process. These include remdesivir, previously used for treatment of the Ebola and hepatitis C viruses and ribavirin, previously used for treatment of respiratory syncytial virus infection, hepatitis C and some hemorrhagic fevers. Remdesivir is reported to target RdRP, whereas ribavirin has been reported to target both 3CLpro and RdRP [2,6,11]. Recently, the US FDA (MD, USA) approved the use of remdesivir for COVID-19 patients aged over 12 years [12]. However, the WHO (Geneva, Switzerland) have released unpublished data from a clinical trial suggesting remdesivir does not reduce the mortality rate, shorten hospital stays or reduce the need for ventilation in patients with severe COVID-19 [1]. Other clinical trials of drug combinations are still ongoing.\u0000 Development of new therapeutic antiviral agents\u0000 The need to develop novel, targeted antivirals to treat SARS-CoV-2 infection is clear. However, the drug discovery and development process is lik","PeriodicalId":73122,"journal":{"name":"Future drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/fdd-2020-0029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43847803","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}
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