scholarly journals Recent Advances in Nanotechnology for the Treatment of Melanoma

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 785
Author(s):  
Roberta Cassano ◽  
Massimo Cuconato ◽  
Gabriella Calviello ◽  
Simona Serini ◽  
Sonia Trombino
Keyword(s):  
Carbon Nanotubes ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Therapeutic Strategies ◽  
Multi Drug Resistance ◽  
Therapeutic Approaches ◽  
Innovative Strategy ◽  
Different Types ◽  
Specific Alternative ◽  
Melanoma Patients

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.

scholarly journals Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4363 ◽  
Author(s):  
Christiana M. Neophytou ◽  
Ioannis P. Trougakos ◽  
Nuray Erin ◽  
Panagiotis Papageorgis
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Family Members ◽  
Multi Drug Resistance ◽  
Tumor Suppressor P53 ◽  
Therapeutic Approaches ◽  
Anti Cancer ◽  
Tumor Phenotype ◽  
Cancer Types ◽  
Apoptotic Pathways

The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types. The PI3K/AKT pathway is pivotal in promoting survival and proliferation and is often overactive in MDR tumors. In addition, the tumor microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit apoptosis in cancer cells and reduce the effectiveness of different anti-cancer drugs. In this review, we describe the main alterations that occur in apoptosis-and related pathways to promote MDR. We also summarize the main therapeutic approaches against resistant tumors, including agents targeting Bcl-2 family members, small molecule inhibitors against IAPs or AKT and agents of natural origin that may be used as monotherapy or in combination with conventional therapeutics. Finally, we highlight the potential of therapeutic exploitation of epigenetic modifications to reverse the MDR phenotype.

scholarly journals The Roles of Extracellular Vesicles in Malignant Melanoma

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2740
Author(s):  
Ying-Chen Cheng ◽  
Yu-An Chang ◽  
Yi-Jen Chen ◽  
Hsu-Min Sung ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Malignant Melanoma ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Bioactive Molecules ◽  
Different Types ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

scholarly journals Integrin-Src-YAP1 signaling mediates the melanoma acquired resistance to MAPK and PI3K/mTOR dual targeted therapy

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Chune Yu ◽  
Min Zhang ◽  
Jinen Song ◽  
Xiaobo Zheng ◽  
Guangchao Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Targeted Therapy ◽  
Acquired Resistance ◽  
Drug Efficacy ◽  
Akt Pathway ◽  
Drug Resistant ◽  
Src Inhibitor ◽  
Melanoma Patients ◽  
Potent Drug ◽  
Dual Drug

Abstract Activation of PI3K/AKT pathway is one of the most recurrent resistant mechanisms for BRAF-targeted therapy, and the combination of MAPK and PI3K/AKT inhibitors becomes one of the most promising regimens for BRAF-targeted relapsed melanoma patients. Although the potent drug efficacy was observed in preclinical experiments and early clinical trials, the dual-drug resistance is inevitable observed. In this study, we systematically explored the mechanisms of dual-drug resistance to MAPKi and PI3K/mTORi in melanoma. With transcriptomic dissection of dual-drug resistant models, we identified that the drug tolerance was mediated by ECM-integrins α3β1 and α11β1 signaling. Upon binding ECM, the integrins activated downstream kinase Src rather than FAK, WNT, or TGFβ. Knockdown of integrins α3, α11, and β1 significantly inhibited the proliferation of dual-drug resistant sublines while with trivial effects on parental cells. Although Src inhibition suppressed the phosphorylation of AKT, c-JUN, and p38, none of inhibitors targeting these kinases reversed the dual-drug resistance in model cells. Notably, Src inhibitor promoted the phosphorylations of LATS1 and YAP1, subsequently, re-localized YAP1 from nucleus to cytosol facilitating further degradation. Both small molecule inhibitors and shRNAs targeting YAP1 or Src overcame the MAPKi and PI3K/mTORi dual-drug resistance. In conclusion, our data not only illuminated an integrin-Src-YAP1 pathway mediated MAPKi and PI3K/mTORi dual-drug resistant mechanism but also provided a potential combinatorial regimen for the drug-relapsed melanoma patients.

scholarly journals Adeno-Associated Viral Vectors as Versatile Tools for Parkinson’s Research, Both for Disease Modeling Purposes and for Therapeutic Uses

2021 ◽  
Vol 22 (12) ◽  
pp. 6389
Author(s):  
Ana Fajardo-Serrano ◽  
Alberto J. Rico ◽  
Elvira Roda ◽  
Adriana Honrubia ◽  
Sandra Arrieta ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Viral Vectors ◽  
Disease Modeling ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Therapeutic Uses ◽  
Different Types ◽  
Experimental Challenge

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson’s disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson’s disease and related synucleinopathies.

scholarly journals Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes

2018 ◽  
Vol 11 (3) ◽  
pp. 84 ◽  
Author(s):  
Ana Gomes ◽  
Ana Moreira ◽  
Gonçalo Mesquita ◽  
Maria Gomes
Keyword(s):  
Iron Metabolism ◽  
Recent Literature ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Different Types ◽  
Essential Nutrient ◽  
Living Organisms ◽  
Almost All ◽  
And Control ◽  
Ongoing Infection

Iron is an essential nutrient for almost all living organisms, but is not easily made available. Hosts and pathogens engage in a fight for the metal during an infection, leading to major alterations in the host’s iron metabolism. Important pathological consequences can emerge from the mentioned interaction, including anemia. Several recent reports have highlighted the alterations in iron metabolism caused by different types of infection, and several possible therapeutic strategies emerge, based on the targeting of the host’s iron metabolism. Here, we review the most recent literature on iron metabolism alterations that are induced by infection, the consequent development of anemia, and the potential therapeutic approaches to modulate iron metabolism in order to correct iron-related pathologies and control the ongoing infection.

scholarly journals Recent novel tumor gatekeepers and potential therapeutic approaches (2017)

2017 ◽  
Vol 16 (10) ◽  
pp. 2545-2553
Author(s):  
Kashif Rafiq Zahid ◽  
Hira Khan Zada ◽  
Ghulam Mustafa Wassan ◽  
Waseem Hassan ◽  
Ke Liu ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Therapeutic Strategies ◽  
Cancer Drugs ◽  
Therapeutic Approaches ◽  
Oncogenic Pathways ◽  
Anti Cancer

Tumor remains a challenging task for oncology community. Drug resistance due to chemotherapy remain principal impediments  toward potential therapeutic strategies. Development of novel anti-cancer drugs or new targeted strategies to conquer drug  resistance is a key goal of cancer research. In this respect, novel tumor gatekeepers and innovative targeted strategies can be  helpful in overcoming drug resistance as well as improve currently used targeted therapies. In this review, efforts have been made to present some of the latest knowledge about novel tumor gatekeepers and new therapeutic strategies to improve the efficacy of  chemotherapy and give new hope to cancer patients to fight against cancer.Keywords: Cancer, Potent inhibitors, Gatekeepers, Therapeutic approaches, Oncogenic pathways

scholarly journals Functionalized Carbon Nanostructures Versus Drug Resistance: Promising Scenarios in Cancer Treatment

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2102 ◽  
Author(s):  
Manuela Curcio ◽  
Annafranca Farfalla ◽  
Federica Saletta ◽  
Emanuele Valli ◽  
Elvira Pantuso ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Drug Resistance ◽  
Carbon Nanostructures ◽  
Multi Drug Resistance ◽  
Biological Mechanisms ◽  
Comprehensive Review ◽  
Biological Features ◽  
Promising Strategy ◽  
Physical Chemical ◽  
Mdr Reversal

Carbon nanostructures (CN) are emerging valuable materials for the assembly of highly engineered multifunctional nanovehicles for cancer therapy, in particular for counteracting the insurgence of multi-drug resistance (MDR). In this regard, carbon nanotubes (CNT), graphene oxide (GO), and fullerenes (F) have been proposed as promising materials due to their superior physical, chemical, and biological features. The possibility to easily modify their surface, conferring tailored properties, allows different CN derivatives to be synthesized. Although many studies have explored this topic, a comprehensive review evaluating the beneficial use of functionalized CNT vs G or F is still missing. Within this paper, the most relevant examples of CN-based nanosystems proposed for MDR reversal are reviewed, taking into consideration the functionalization routes, as well as the biological mechanisms involved and the possible toxicity concerns. The main aim is to understand which functional CN represents the most promising strategy to be further investigated for overcoming MDR in cancer.

scholarly journals Combined targeted therapy and immunotherapy in melanoma: a review of the impact on the tumor microenvironment and outcomes of early clinical trials

2019 ◽  
Vol 11 ◽  
pp. 175883591983082 ◽  
Author(s):  
Meredith S. Pelster ◽  
Rodabe N. Amaria
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Tumor Microenvironment ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Therapeutic Approaches ◽  
T Cell Infiltration ◽  
Melanoma Patients ◽  
The Impact ◽  
Preclinical Work

The development of BRAF and MEK inhibitors (BRAFis and MEKis) and immune checkpoint inhibitors have changed the management of advanced stage melanoma and improved the outcomes of patients with this malignancy. However, both therapeutic approaches have limitations, including a limited duration of benefit in subsets of BRAF-mutant melanoma patients treated with targeted therapy and a lower overall response rate without a clear predictive biomarker in patients treated with checkpoint inhibitors. Preclinical and translational data have shown that BRAFis and MEKis alter the tumor microenvironment to make it more amenable to immunotherapy and have provided the scientific rationale for combing BRAFis and MEKis with immunotherapy. In this review, the initial studies demonstrating the impact of BRAFis and MEKis on the expression of melanoma differentiation antigens, T-cell infiltration, and the balance of immune stimulatory and immune suppressive cells and cytokines are addressed. Preclinical work on the combination of targeted therapy with BRAFis and MEKis with immunotherapy are reviewed, highlighting improved tumor responses in mouse models of BRAF-mutated melanoma treated with combinatorial strategies. Lastly, data from early clinical trials of combined targeted therapy and immunotherapy are discussed, focusing on response rates and toxicities.

scholarly journals Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules

2021 ◽  
Vol 14 (8) ◽  
pp. 803
Author(s):  
Federica Tonon ◽  
Rossella Farra ◽  
Cristina Zennaro ◽  
Gabriele Pozzato ◽  
Nhung Truong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Husbandry ◽  
Therapeutic Strategies ◽  
Common Type ◽  
Transgenic Zebrafish ◽  
Therapeutic Approaches ◽  
Predisposing Factor ◽  
Different Types ◽  
Xenograft Models ◽  
Tumor Related Death

Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.

Sign in / Sign up

Export Citation Format

Share Document