scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

scholarly journals Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines

2009 ◽  
Vol 05 (01) ◽  
pp. 40
Author(s):  
Adam Yagui-Beltrán ◽  
Lisa M Coussens ◽  
David M Jablons ◽  
◽  
◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Lung Carcinogenesis ◽  
Respiratory Homeostasis ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumorassociated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

scholarly journals Neuroprotective Potential of GDF11: Myth or Reality?

2019 ◽  
Vol 20 (14) ◽  
pp. 3563 ◽  
Author(s):  
Luc Rochette ◽  
Gabriel Malka
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Plasma ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Therapeutic Strategies ◽  
Blood Concentrations ◽  
Age Related ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Novel Therapeutic

In the brain, aging is accompanied by cellular and functional deficiencies that promote vulnerability to neurodegenerative disorders. In blood plasma from young and old animals, various factors such as growth differentiation factor 11 (GDF11), whose levels are elevated in young animals, have been identified. The blood concentrations of these factors appear to be inversely correlated with the age-related decline of neurogenesis. The identification of GDF11 as a “rejuvenating factor” opens up perspectives for the treatment of neurodegenerative diseases. As a pro-neurogenic and pro-angiogenic agent, GDF11 may constitute a basis for novel therapeutic strategies.

scholarly journals VGLUT modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration

2020 ◽  
Author(s):  
Silas A. Buck ◽  
Thomas Steinkellner ◽  
Despoina Aslanoglou ◽  
Michael Villeneuve ◽  
Sai H. Bhatte ◽  
...  
Keyword(s):  
Sex Differences ◽  
Risk Factor ◽  
Glutamate Transporter ◽  
Therapeutic Strategies ◽  
Dependent Manner ◽  
Vesicular Glutamate Transporter ◽  
Progressive Loss ◽  
Age Related ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Age is the greatest risk factor for Parkinson’s disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. We found that vesicular glutamate transporter (VGLUT) expression mediates vulnerability to age-related DA neurodegeneration in a sex-dependent manner, providing a new mechanism for sex differences in selective DA neuron vulnerability. These findings lay the groundwork for novel therapeutic strategies to boost neuronal resilience throughout aging.

scholarly journals TCR-like antibodies in cancer immunotherapy

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Qinghua He ◽  
Zhaoyu Liu ◽  
Zhihua Liu ◽  
Yuxiong Lai ◽  
Xinke Zhou ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
T Cell Receptor ◽  
Molecular Mechanisms ◽  
Antibody Therapy ◽  
Cell Receptor ◽  
Therapeutic Strategies ◽  
Cell Surfaces ◽  
The Core ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Abstract Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.

scholarly journals Novel Insights into Molecular Mechanisms of Chronic Pain

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2220
Author(s):  
Ellen Niederberger
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Special Issue ◽  
Different Types ◽  
Chronic Pain Conditions ◽  
Novel Therapeutic Strategies ◽  
Pain Patients ◽  
Novel Therapeutic

Pain is the most frequent cause triggering patients to visit a physician. The worldwide incidence of chronic pain is in the range of 20% of adults, and chronic pain conditions are frequently associated with several comorbidities and a drastic decrease in patients’ quality of life. Although several approved analgesics are available, such therapy is often not satisfying due to insufficient efficacy and/or severe side effects. Therefore, novel strategies for the development of safe and highly efficacious pain killers are urgently needed. To reach this goal, it is necessary to clarify the causes and signal transduction cascades underlying the onset and progression of the different types of chronic pain. The papers in this Special Issue cover a wide variety of mechanisms involved in different pain types such as inflammatory, neuropathic or cancer pain. Therefore, the results summarized here might contribute to a better understanding of the mechanisms in chronic pain and thereby to the development of novel therapeutic strategies for pain patients.

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