Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Mukherjee A
PROVIDER: S-EPMC7013812 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Ovarian cancer is a deadly malignancy with a growing therapeutic armamentarium, though achieving sustained benefit in the clinic remains largely elusive. Through biomarker and genetic analysis, several pathways of resistance and sensitivity to commonly used therapeutics have been identified, expanding the potential of identifying unique drug combinations and indicating new directions for improving clinical outcomes. Here, we review the mechanisms of angiogenic response and antiangiogenic therapy in ovarian cancer, as well as the interactions it exhibits with the immune and DNA damage response pathways. We discuss results from clinical trials examining the combinations of antiangiogenics, PARP inhibitors, and immune checkpoint inhibitors are also discussed, as well as several ongoing trials.
| S-EPMC8217312 | biostudies-literature
Project description:Although current anticancer immunotherapies using immune checkpoint inhibitors (ICIs) have been reported with a high clinical success rate, numerous patients still bear 'cold' tumors with insufficient T cell infiltration and low immunogenicity, responding poorly to ICI therapy. Considering the advancements in precision medicine, in-depth mechanism studies on the tumor immune microenvironment (TIME) among cold tumors are required to improve the treatment for these patients. Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy, activates immune function, modulates the TIME, and has been applied in combination with other anticancer therapeutic strategies. This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies, as well as a brief talk about the feasibility of clinical translation.
| S-EPMC8006526 | biostudies-literature
Project description:Poly(ADP-ribose) polymerase inhibitors (PARPi) are a new class of agents with unparalleled clinical achievement for driving synthetic lethality in BRCA-deficient cancers. Recent FDA approval of PARPi has motivated clinical trials centered around the optimization of PARPi-associated therapies in a variety of BRCA-deficient cancers. This review highlights recent advancements in understanding the molecular mechanisms of PARP 'trapping' and synthetic lethality. Particular attention is placed on the potential extension of PARPi therapies from BRCA-deficient patients to populations with other homologous recombination-deficient backgrounds, and common characteristics of PARPi and non-homologous end-joining have been elucidated. The synergistic antitumor effect of combining PARPi with various immune checkpoint blockades has been explored to evaluate the potential of combination therapy in attaining greater therapeutic outcome. This has shed light onto the differing classifications of PARPi as well as the factors that result in altered PARPi activity. Lastly, acquired chemoresistance is a crucial issue for clinical application of PARPi. The molecular mechanisms underlying PARPi resistance and potential overcoming strategies are discussed.
| S-EPMC7501589 | biostudies-literature
Project description:Hereditary retinal dystrophies (HRDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision, and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles, with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family, highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been proposed as potentially efficacious therapies. Because of its favorable anatomical and immunological characteristics, the eye has been at the forefront of translational gene therapy. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Dozens of promising proofs of concept have been obtained in animal models of HRDs and some of them have been relayed to the clinic. The results from the first clinical trials for a congenital form of blindness have generated great interest and have demonstrated the safety and efficacy of intraocular administrations of viral vectors in humans. This review summarizes the clinical development of retinal gene therapy.
| S-EPMC5758769 | biostudies-literature
Project description:The central importance of angiogenesis and our understanding of how new blood vessels are formed have led to the development of novel antiangiogenic therapies. Although the number of agents in development has grown exponentially, only one phase III trial in breast cancer has been completed. In that study the addition of bevacizumab to capecitabine did not extend the progression-free survival of patients with refractory disease as compared with capecitabine monotherapy. Early enthusiasm for antiangiogenic therapy must give way to clinical reality. Our challenge now is to exploit better the activity of antiangiogenic agents seen in the early clinical studies.
| S-EPMC400679 | biostudies-literature
Project description:Cancer is the second biggest cause of death in children in the US. With the development of chemotherapy, there has been a substantial increase in the overall survival rate in the last 30 years. However, the overall mortality rate in children with cancer remains 25%, and many survivors experience a decline in overall quality of life and long-term adverse effects caused by treatments. Although cancer cells share common characteristics, pediatric cancers are different from adult cancers in their prevalence, mutation load, and drug response. Therefore, there is an urgent unmet need to develop therapeutic approaches specifically designed for children with cancer. Nanotechnology can potentially overcome the deficiencies of conventional methods of administering chemotherapy and ultimately improve clinical outcomes. The nanoparticle-based drug delivery systems can decrease the toxicity of therapy, provide a sustained or controlled drug release, improve the pharmacokinetic properties of loading contents, and achieve a targeted drug delivery with achievable modifications. Furthermore, therapeutic approaches based on combining nanoformulated drugs with novel immunotherapeutic agents are emerging. In this review, we discussed the recently developed nanotechnology-based strategies for treating blood and solid pediatric cancers.
| S-EPMC8036287 | biostudies-literature
Project description:Cancer remains an obstacle to be surmounted by humans. As an FDA-approved biocompatible drug excipient, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely applied in drug delivery system (DDS). Along with in-depth analyses of TPGS-based DDS, increasingly attractive results have revealed that TPGS is able to act not only as a simple drug carrier but also as an assistant molecule with various bio-functions to improve anticancer efficacy. In this review, recent advances in TPGS-based DDS are summarized. TPGS can inhibit P-glycoprotein, enhance drug absorption, induce mitochondrial-associated apoptosis or other apoptotic pathways, promote drug penetration and tumor accumulation, and even inhibit tumor metastasis. As a result, many formulations, by using original TPGS, TPGS-drug conjugates or TPGS copolymers, were prepared, and as expected, an enhanced therapeutic effect was achieved in different tumor models, especially in multidrug resistant and metastatic tumors. Although the mechanisms by which TPGS participates in such functions are not yet very clear, considering its effectiveness in tumor treatment, TPGS-based DDS appears to be one of the best candidates for future clinical applications.
| S-EPMC8241040 | biostudies-literature
Project description:Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria.
| S-EPMC3096961 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2), previously called 2019 novel CoV, emerged from China in late December 2019. This virus causes CoV disease-19 (COVID-19), which has been proven a global pandemic leading to a major outbreak. As of June 19, 2020, the data from the World Health Organization (WHO) showed more than 8.7 million confirmed cases in over 200 countries/regions. The WHO has declared COVID-19 as the sixth public health emergency of international concern on January 30, 2020. CoVs cause illnesses that range in severity from the common cold to severe respiratory illnesses and death. Nevertheless, with technological advances and imperative lessons gained from prior outbreaks, humankind is better outfitted to deal with the latest emerging group of CoVs. Studies on the development of in vitro diagnostic tests, vaccines, and drug re-purposing are being carried out in this field. Currently, no approved treatment is available for SARS-CoV-2 given the lack of evidence. The results from preliminary clinical trials have been mixed as far as improvement in the clinical condition and reduction in the duration of treatment are concerned. A number of new clinical trials are currently in progress to test the efficacy and safety of various approved drugs. This review focuses on recent advancements in the field of development of diagnostic tests, vaccines, and treatment approaches for COVID-19.
| S-EPMC7381292 | biostudies-literature
Project description:Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil® (liposomal doxorubicin) in 1995 to Onivyde® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale-up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical trials, and the challenges that may hinder development of the nanomedicines for cancer treatment.
| S-EPMC5725398 | biostudies-other