Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due...Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows (Tymianski, 2017). Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis (Bernstock et al., 2018a). With the success of recent endovascular thrombectomy (EVT) trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity (i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation), restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window (i.e., when they still have salvageable brain tissue) (Tymianski, 2017). Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.展开更多
Globally, cancer is growing at an alarming pace, which calls for development of more efficient cancer treatments. Conventional chemotherapy and radiotherapy have become crucial first-line clinical treatments for cance...Globally, cancer is growing at an alarming pace, which calls for development of more efficient cancer treatments. Conventional chemotherapy and radiotherapy have become crucial first-line clinical treatments for cancer. However, along with their wide usage, limited therapeutic effects, severe adverse reactions, unaffordable costs, and complicated operations lead to failures of these treat- ments. Moreover, the emergence of multidrug resistance inhibits the longtirne usage of chemotherapeutics. One of the major causes of treatment failure is the insufficient sensitivity of cancer cells to therapeutic drugs or treatments. With the rigorous development of nanotechnolog~ tailored nanoparticles can efficiently sensitize malignant cells by inducing intracellular structural and functional changes, which could affect vital intracellular processes such as metabolism, signal conduction, proliferation, cell death as well as intracellular drug delivery. Here, we review recent advances in nanomaterial-assisted sensitization of oncotherapy, and challenges and strategies in the development of nanomedical approaches.展开更多
Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical...Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs.ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development.It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells,thereby producing promising antitumor efficacy and favorable adverse effect profiles.However,emergence of drug resistance has severely hindered the clinical efficacy of ADCs.In this review,we introduce the structure and mechanism of ADCs,describe the development of ADCs,summarized the latest research about the mechanisms of ADC resistance,discussed the strategies to overcome ADCs resistance,and predicted biomarkers for treatment response to ADC,aiming to contribute to the development of ADCs in the future.展开更多
Fatty acid oxidation(FAO)denotes the mitochondrial aerobic process responsible for breaking down fatty acids(FAs)into acetyl-CoA units.This process holds a central position in the cancer metabolic landscape,with certa...Fatty acid oxidation(FAO)denotes the mitochondrial aerobic process responsible for breaking down fatty acids(FAs)into acetyl-CoA units.This process holds a central position in the cancer metabolic landscape,with certain tumor cells relying primarily on FAO for energy production.Over the past decade,mounting evidence has underscored the critical role of FAO in various cellular processes such as cell growth,epigenetic modifications,tissue-immune ho-meostasis,cell signal transduction,and more.FAO is tightly regulated by multiple evolution-arily conserved mechanisms,and any dysregulation can predispose to cancer development.In this view,we summarize recent findings to provide an updated understanding of the multi-faceted roles of FAO in tumor development,metastasis,and the response to cancer therapy.Additionally,we explore the regulatory mechanisms of FAO,laying the groundwork for poten-tial therapeutic interventions targeting FAO in cancers within the metabolic landscape.展开更多
文摘Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows (Tymianski, 2017). Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis (Bernstock et al., 2018a). With the success of recent endovascular thrombectomy (EVT) trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity (i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation), restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window (i.e., when they still have salvageable brain tissue) (Tymianski, 2017). Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.
文摘Globally, cancer is growing at an alarming pace, which calls for development of more efficient cancer treatments. Conventional chemotherapy and radiotherapy have become crucial first-line clinical treatments for cancer. However, along with their wide usage, limited therapeutic effects, severe adverse reactions, unaffordable costs, and complicated operations lead to failures of these treat- ments. Moreover, the emergence of multidrug resistance inhibits the longtirne usage of chemotherapeutics. One of the major causes of treatment failure is the insufficient sensitivity of cancer cells to therapeutic drugs or treatments. With the rigorous development of nanotechnolog~ tailored nanoparticles can efficiently sensitize malignant cells by inducing intracellular structural and functional changes, which could affect vital intracellular processes such as metabolism, signal conduction, proliferation, cell death as well as intracellular drug delivery. Here, we review recent advances in nanomaterial-assisted sensitization of oncotherapy, and challenges and strategies in the development of nanomedical approaches.
基金supported by the National Natural Science Foundation of China(Nos.U21A20421 and 82073882)the Key Project of Science Technology Program of Guangzhou(No.2023B03J0029)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515130009)Key-Area Research and Development Program of Guangdong Province(2023B1111020005).
文摘Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs.ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development.It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells,thereby producing promising antitumor efficacy and favorable adverse effect profiles.However,emergence of drug resistance has severely hindered the clinical efficacy of ADCs.In this review,we introduce the structure and mechanism of ADCs,describe the development of ADCs,summarized the latest research about the mechanisms of ADC resistance,discussed the strategies to overcome ADCs resistance,and predicted biomarkers for treatment response to ADC,aiming to contribute to the development of ADCs in the future.
文摘Fatty acid oxidation(FAO)denotes the mitochondrial aerobic process responsible for breaking down fatty acids(FAs)into acetyl-CoA units.This process holds a central position in the cancer metabolic landscape,with certain tumor cells relying primarily on FAO for energy production.Over the past decade,mounting evidence has underscored the critical role of FAO in various cellular processes such as cell growth,epigenetic modifications,tissue-immune ho-meostasis,cell signal transduction,and more.FAO is tightly regulated by multiple evolution-arily conserved mechanisms,and any dysregulation can predispose to cancer development.In this view,we summarize recent findings to provide an updated understanding of the multi-faceted roles of FAO in tumor development,metastasis,and the response to cancer therapy.Additionally,we explore the regulatory mechanisms of FAO,laying the groundwork for poten-tial therapeutic interventions targeting FAO in cancers within the metabolic landscape.
