Role of Opioids in Fibromyalgia and Its Resistance to Therapy

Pain Medicine ◽  
2020 ◽  
Vol 21 (10) ◽  
pp. 2059-2060
Author(s):  
Bruce Rothschild
Keyword(s):  
Resistance To Therapy

scholarly journals Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Meilin Chan ◽  
Licun Wu ◽  
Zhihong Yun ◽  
Trevor D. McKee ◽  
Michael Cabanero ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Malignant Pleural Mesothelioma ◽  
Neutralizing Antibodies ◽  
Pleural Mesothelioma ◽  
Spheroid Formation ◽  
Resistance To Therapy ◽  
Sarcomatoid Mesothelioma

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

scholarly journals Regulation and pharmacological targeting of RAD51 in cancer

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
McKenzie K Grundy ◽  
Ronald J Buckanovich ◽  
Kara A Bernstein
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Patient Outcomes ◽  
Cancer Biology ◽  
Cancer Resistance ◽  
Breast And Ovarian Cancer ◽  
Resistance To Therapy ◽  
Damage Repair

Abstract Regulation of homologous recombination (HR) is central for cancer prevention. However, too little HR can increase cancer incidence, whereas too much HR can drive cancer resistance to therapy. Importantly, therapeutics targeting HR deficiency have demonstrated a profound efficacy in the clinic improving patient outcomes, particularly for breast and ovarian cancer. RAD51 is central to DNA damage repair in the HR pathway. As such, understanding the function and regulation of RAD51 is essential for cancer biology. This review will focus on the role of RAD51 in cancer and beyond and how modulation of its function can be exploited as a cancer therapeutic.

scholarly journals Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 136 ◽  
Author(s):  
Clodagh O’Neill ◽  
Katie Gilligan ◽  
Róisín Dwyer
Keyword(s):  
Disease Progression ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Underlying Disease ◽  
Cell Stress ◽  
Response To Therapy ◽  
Nanosized Particles ◽  
Resistance To Therapy ◽  
Cell Stress Response

Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed.

scholarly journals Sphingolipid/Ceramide Pathways and Autophagy in the Onset and Progression of Melanoma: Novel Therapeutic Targets and Opportunities

2019 ◽  
Vol 20 (14) ◽  
pp. 3436 ◽  
Author(s):  
Michele Lai ◽  
Veronica La Rocca ◽  
Rachele Amato ◽  
Giulia Freer ◽  
Mauro Pistello
Keyword(s):  
Stem Cells ◽  
Skin Cancer ◽  
Early Diagnosis ◽  
Molecular Targets ◽  
Neoplastic Transformation ◽  
Resistance To Therapy ◽  
Advanced Stages ◽  
Efficient Elimination ◽  
Novel Therapeutic

Melanoma is a malignant tumor deriving from neoplastic transformation of melanocytes. The incidence of melanoma has increased dramatically over the last 50 years. It accounts for most cases of skin cancer deaths. Early diagnosis leads to remission in 90% of cases of melanoma; conversely, for melanoma at more advanced stages, prognosis becomes more unfavorable also because dvanced melanoma is often resistant to pharmacological and radiological therapies due to genetic plasticity, presence of cancer stem cells that regenerate the tumor, and efficient elimination of drugs. This review illustrates the role of autophagy in tumor progression and resistance to therapy, focusing on molecular targets for future drugs.

The role of metabolism and tunneling nanotube-mediated intercellular mitochondria exchange in cancer drug resistance

2018 ◽  
Vol 475 (14) ◽  
pp. 2305-2328 ◽  
Author(s):  
Yalda Hekmatshoar ◽  
Jean Nakhle ◽  
Mireille Galloni ◽  
Marie-Luce Vignais
Keyword(s):  
Drug Resistance ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Cancer Drug ◽  
Special Focus ◽  
Cellular Interactions ◽  
Tunneling Nanotubes ◽  
Resistance To Therapy ◽  
Cancer Drug Resistance

Intercellular communications play a major role in tissue homeostasis. In pathologies such as cancer, cellular interactions within the tumor microenvironment (TME) contribute to tumor progression and resistance to therapy. Tunneling nanotubes (TNTs) are newly discovered long-range intercellular connections that allow the exchange between cells of various cargos, ranging from ions to whole organelles such as mitochondria. TNT-transferred mitochondria were shown to change the metabolism and functional properties of recipient cells as reported for both normal and cancer cells. Metabolic plasticity is now considered a hallmark of cancer as it notably plays a pivotal role in drug resistance. The acquisition of cancer drug resistance was also associated to TNT-mediated mitochondria transfer, a finding that relates to the role of mitochondria as a hub for many metabolic pathways. In this review, we first give a brief overview of the various mechanisms of drug resistance and of the cellular communication means at play in the TME, with a special focus on the recently discovered TNTs. We further describe recent studies highlighting the role of the TNT-transferred mitochondria in acquired cancer cell drug resistance. We also present how changes in metabolic pathways, including glycolysis, pentose phosphate and lipid metabolism, are linked to cancer cell resistance to therapy. Finally, we provide examples of novel therapeutic strategies targeting mitochondria and cell metabolism as a way to circumvent cancer cell drug resistance.

scholarly journals Pathogenesis beyond the cancer clone(s) in multiple myeloma

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3049-3058 ◽  
Author(s):  
Giada Bianchi ◽  
Nikhil C. Munshi
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clonal Evolution ◽  
Bone Marrow Microenvironment ◽  
Plasma Cell Dyscrasia ◽  
Cancer Microenvironment ◽  
Resistance To Therapy ◽  
Cancer Pathogenesis ◽  
The Impact

Abstract Over the past 4 decades, basic research has provided crucial information regarding the cellular and molecular biology of cancer. In particular, the relevance of cancer microenvironment (including both cellular and noncellular elements) and the concept of clonal evolution and heterogeneity have emerged as important in cancer pathogenesis, immunologic escape, and resistance to therapy. Multiple myeloma (MM), a cancer of terminally differentiated plasma cells, is emblematic of the impact of cancer microenvironment and the role of clonal evolution. Although genetic and epigenetic aberrations occur in MM and evolve over time under the pressure of exogenous stimuli, they are also largely present in premalignant plasma cell dyscrasia such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), suggesting that genetic mutations alone are necessary, but not sufficient, for myeloma transformation. The role of bone marrow microenvironment in mediating survival, proliferation, and resistance to therapy in myeloma is well established; and although an appealing speculation, its role in fostering the evolution of MGUS or SMM into MM is yet to be proven. In this review, we discuss MM pathogenesis with a particular emphasis on the role of bone marrow microenvironment.

scholarly journals The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy

Hypoxia ◽  
2015 ◽  
pp. 83 ◽  
Author(s):  
Barbara Muz ◽  
Pilar de la Puente ◽  
Feda Azab ◽  
Abdel K. Azab
Keyword(s):  
Cancer Progression ◽  
Resistance To Therapy

scholarly journals The role of cancer stem cells in tumor heterogeneity and resistance to therapy

2017 ◽  
Vol 95 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Christina Valbirk Konrad ◽  
Reshma Murali ◽  
Binitha Anu Varghese ◽  
Radhika Nair
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Therapy Resistance ◽  
Cellular Mechanisms ◽  
Resistance To Therapy ◽  
Repair Mechanisms ◽  
Cancer Types ◽  
Survival Signaling

Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients. The cellular mechanisms of therapy resistance in CSCs are ascribed to several factors including a state of quiescence, an enhanced DNA damage response and active repair mechanisms, up-regulated expression of drug efflux transporters, as well as the activation of pro-survival signaling pathways and inactivation of apoptotic signaling. Understanding the mechanisms underlying the acquisition of resistance to therapy may hold the key to targeting the CSC population.

scholarly journals The multifaceted role of lemur tyrosine kinase 3 in health and disease

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Angeliki Ditsiou ◽  
Teresa Gagliano ◽  
Mark Samuels ◽  
Viviana Vella ◽  
Christos Tolias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Treatment ◽  
Physiological Function ◽  
Receptor Trafficking ◽  
Signalling Pathways ◽  
Resistance To Therapy ◽  
Important Player ◽  
Health And Disease

In the last decade, LMTK3 (lemur tyrosine kinase 3) has emerged as an important player in breast cancer, contributing to the advancement of disease and the acquisition of resistance to therapy through a strikingly complex set of mechanisms. Although the knowledge of its physiological function is largely limited to receptor trafficking in neurons, there is mounting evidence that LMTK3 promotes oncogenesis in a wide variety of cancers. Recent studies have broadened our understanding of LMTK3 and demonstrated its importance in numerous signalling pathways, culminating in the identification of a potent and selective LMTK3 inhibitor. Here, we review the roles of LMTK3 in health and disease and discuss how this research may be used to develop novel therapeutics to advance cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document