scholarly journals Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

2020 ◽  
Vol 9 (10) ◽  
pp. 3226
Author(s):  
Cristina Belgiovine ◽  
Elisabeth Digifico ◽  
Clément Anfray ◽  
Aldo Ummarino ◽  
Fernando Torres Andón
Keyword(s):  
Current Knowledge ◽  
Cancer Therapies ◽  
Combination Therapies ◽  
Tumor Associated Macrophages ◽  
Effector Cells ◽  
Anti Cancer ◽  
Novel Therapeutic Strategies ◽  
The Right ◽  
Do The Right Thing ◽  
Cytotoxic Effector

In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.

Stress responses as master keys to epigenomic changes in transcriptome and metabolome for cancer etiology and therapeutics

2021 ◽  
Author(s):  
Atanu Mondal ◽  
Apoorva Bhattacharya ◽  
Vipin Singh ◽  
Shruti Pandita ◽  
Albino Bacolla ◽  
...  
Keyword(s):  
Stress Response ◽  
Cancer Cells ◽  
Stress Responses ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
Molecular Architecture ◽  
Cancer Etiology ◽  
Treatment Scenario ◽  
Anti Cancer ◽  
Novel Therapeutic Strategies

From initiation through progression, cancer cells are subjected to a magnitude of endogenous and exogenous stresses, which aid in their neoplastic transformation. Exposure to these classes of stress induces imbalance in cellular homeostasis and, in response, cancer cells employ informative adaptive mechanisms to rebalance biochemical processes that facilitate survival and maintain their existence. Different kinds of stress stimuli trigger epigenetic alterations in cancer cells, which leads to changes in their transcriptome and metabolome, ultimately resulting in suppression of growth inhibition or induction of apoptosis. Whether cancer cells show a protective response to stress or succumb to cell death depends on the type of stress and duration of exposure. A thorough understanding of epigenetic and molecular architecture of cancer cell stress response pathways can unveil a plethora of information required to develop novel anti-cancer therapeutics. The present view highlights current knowledge about alterations in epigenome and transcriptome of cancer cells as a consequence of exposure to different physicochemical stressful stimuli such as reactive oxygen species (ROS), hypoxia, radiation, hyperthermia, genotoxic agents, and nutrient deprivation. Currently, an anti-cancer treatment scenario involving the imposition of stress on target cancer cells is gaining traction to augment or even replace conventional therapeutic regimens. Therefore, a comprehensive understanding of stress response pathways is crucial for devising and implementing novel therapeutic strategies.

scholarly journals Therapeutic Perspectives of Molecules from Urtica dioica Extracts for Cancer Treatment

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2753 ◽  
Author(s):  
Sabrina Esposito ◽  
Alessandro Bianco ◽  
Rosita Russo ◽  
Antimo Di Maro ◽  
Carla Isernia ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Biological Activities ◽  
Urtica Dioica ◽  
Cancer Therapies ◽  
Edible Plant ◽  
Bioactive Natural Products ◽  
Human Cancers ◽  
Anti Cancer

A large range of chronic and degenerative diseases can be prevented through the use of food products and food bioactives. This study reports the health benefits and biological activities of the Urtica dioica (U. dioica) edible plant, with particular focus on its cancer chemopreventive potential. Numerous studies have attempted to investigate the most efficient anti-cancer therapy with few side effects and high toxicity on cancer cells to overcome the chemoresistance of cancer cells and the adverse effects of current therapies. In this regard, natural products from edible plants have been assessed as sources of anti-cancer agents. In this article, we review current knowledge from studies that have examined the cytotoxic, anti-tumor and anti-metastatic effects of U. dioica plant on several human cancers. Special attention has been dedicated to the treatment of breast cancer, the most prevalent cancer among women and one of the main causes of death worldwide. The anti-proliferative and apoptotic effects of U. dioica have been demonstrated on different human cancers, investigating the properties of U. dioica at cellular and molecular levels. The potent cytotoxicity and anti-cancer activity of the U. dioica extracts are due to its bioactive natural products content, including polyphenols which reportedly possess anti-oxidant, anti-mutagenic and anti-proliferative properties. The efficacy of this edible plant to prevent or mitigate human cancers has been demonstrated in laboratory conditions as well as in experimental animal models, paving the way to the development of nutraceuticals for new anti-cancer therapies.

scholarly journals The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Kate Dinneen ◽  
Anne-Marie Baird ◽  
Ciara Ryan ◽  
Orla Sheils
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Gastroesophageal Junction ◽  
Western World ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Anti Cancer

Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance.

Combination Therapies of Artemisinin and its Derivatives as a Viable Approach for Future Cancer Treatment

2019 ◽  
Vol 25 (31) ◽  
pp. 3323-3338 ◽  
Author(s):  
Maushmi S. Kumar ◽  
Tanuja T. Yadav ◽  
Rohan R. Khair ◽  
Godefridus J. Peters ◽  
Mayur C. Yergeri
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Steroid Receptors ◽  
Deep Understanding ◽  
Breast Cancer Cell Lines ◽  
Extensive Literature ◽  
Cancer Therapies ◽  
Combination Therapies ◽  
Cytotoxicity Activity ◽  
Anti Cancer

Background: Many anticancer drugs have been developed for clinical usage till now, but the major problem is the development of drug-resistance over a period of time in the treatment of cancer. Anticancer drugs produce huge adverse effects, ultimately leading to death of the patient. Researchers have been focusing on the development of novel molecules with higher efficacy and lower toxicity; the anti-malarial drug artemisinin and its derivatives have exhibited cytotoxic effects. Methods: We have done extensive literature search for artemisinin for its new role as anti-cancer agent for future treatment. Last two decades papers were referred for deep understanding to strengthen its role. Results: Literature shows changes at 9, 10 position in the artemisinin structure produces anticancer activity. Artemisinin shows anticancer activity in leukemia, hepatocellular carcinoma, colorectal and breast cancer cell lines. Artemisinin and its derivatives have been studied as combination therapy with several synthetic compounds, RNA interfaces, recombinant proteins and antibodies etc., for synergizing the effect of these drugs. They produce an anticancer effect by causing cell cycle arrest, regulating signaling in apoptosis, angiogenesis and cytotoxicity activity on the steroid receptors. Many novel formulations of artemisinin are being developed in the form of carbon nanotubes, polymer-coated drug particles, etc., for delivering artemisinin, since it has poor water/ oil solubility and is chemically unstable. Conclusion: We have summarize the combination therapies of artemisinin and its derivatives with other anticancer drugs and also focussed on recent developments of different drug delivery systems in the last 10 years. Various reports and clinical trials of artemisinin type drugs indicated selective cytotoxicity along with minimal toxicity thus projecting them as promising anti-cancer agents in future cancer therapies.

scholarly journals Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies

2021 ◽  
Vol 11 ◽  
Author(s):  
Malina Xiao ◽  
Alice Benoit ◽  
Meriem Hasmim ◽  
Caroline Duhem ◽  
Guillaume Vogin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Therapeutic Benefit ◽  
Cancer Therapies ◽  
Cancer Resistance ◽  
Tumor Resistance ◽  
Anti Cancer ◽  
Almost All ◽  
The Impact

Autophagy is a highly regulated multi-step process that occurs at the basal level in almost all cells. Although the deregulation of the autophagy process has been described in several pathologies, the role of autophagy in cancer as a cytoprotective mechanism is currently well established and supported by experimental and clinical evidence. Our understanding of the molecular mechanism of the autophagy process has largely contributed to defining how we can harness this process to improve the benefit of cancer therapies. While the role of autophagy in tumor resistance to chemotherapy is extensively documented, emerging data point toward autophagy as a mechanism of cancer resistance to radiotherapy, targeted therapy, and immunotherapy. Therefore, manipulating autophagy has emerged as a promising strategy to overcome tumor resistance to various anti-cancer therapies, and autophagy modulators are currently evaluated in combination therapies in several clinical trials. In this review, we will summarize our current knowledge of the impact of genetically and pharmacologically modulating autophagy genes and proteins, involved in the different steps of the autophagy process, on the therapeutic benefit of various cancer therapies. We will also briefly discuss the challenges and limitations to developing potent and selective autophagy inhibitors that could be used in ongoing clinical trials.

scholarly journals Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 46 ◽  
Author(s):  
Anfray ◽  
Ummarino ◽  
Andón ◽  
Allavena
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Response ◽  
Current Knowledge ◽  
Tumor Associated Macrophages ◽  
Cancer Proliferation ◽  
The Past ◽  
Active Research ◽  
Novel Therapeutic Strategies

: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

scholarly journals Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1

2020 ◽  
Author(s):  
Eduardo Salido ◽  
David J. Timson ◽  
Isabel Betancor-Fernández ◽  
Rogelio Palomino-Morales ◽  
Angel L. Pey
Keyword(s):  
Associated Factors ◽  
Current Knowledge ◽  
Cancer Development ◽  
Cancer Therapies ◽  
Pharmacological Modulation ◽  
Oxygen Homeostasis ◽  
Anti Cancer ◽  
Molecular Determinants ◽  
The Stability ◽  
Alpha Function

HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that HIF-1α interaction with NQO1 inhibits its proteasomal degradation, thus suggesting that targeting the stability of NQO1 could led to destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, we review here our current knowledge on the intracellular functions and stability of NQO1, its pharmacological modulation by small ligands, and the molecular determinants of its roles as a chaperone of many different proteins including cancer-associated factors such as p53 and p73α. This knowledge is then discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies.

Puzzling and ambivalent roles of malarial infections in cancer development and progression

Parasitology ◽  
2016 ◽  
Vol 143 (14) ◽  
pp. 1811-1823 ◽  
Author(s):  
ERIC FAURE
Keyword(s):  
Epstein Barr Virus ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Cancer Therapies ◽  
Virus Reactivation ◽  
Open Future ◽  
Barr Virus ◽  
Anti Cancer ◽  
Causative Agents ◽  
Epstein Barr

SUMMARYScientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth.Plasmodiumprotozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans,Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

microRNA in the control of stem-like phenotype of cancer cells

2013 ◽  
Vol 8 (10) ◽  
pp. 931-942 ◽  
Author(s):  
Michal Wozniak
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Small Subset ◽  
Cancer Therapies ◽  
Aberrant Expression ◽  
Self Renewal ◽  
Anti Cancer ◽  
Current Therapies

AbstractCurrent therapies against metastatic tumors are still ineffective. Cancer stem cells — a small subset of cells inside the tumor that possesses a self-renewal capacity — might be responsible for the recurrence of the tumor after anti-cancer therapies. Their immortality and unique drug resistance impede their eradication during therapy. The ‘stemness’ of these cells is controlled by microRNAs. These molecules possess the ability to downregulate gene expression by binding to the target mRNA. It turns out that microRNAs control the expression of approximately 60% of the genes in human cells. MicroRNA aberrant expression can lead to cancer development and progression. Therefore, recent research has focused on unraveling the role of microRNA in maintaining a stem-like phenotype in malignant tumors and cancer stem cells. This review summarizes our current knowledge about microRNAs that control the self-renewal capacity of cancer stem cells and indicates the importance of profound research aimed at developing efficient miRNA-targeted therapies.

scholarly journals Myeloid-derived suppressor cells and their role in gynecological malignancies

Tumor Biology ◽  
2018 ◽  
Vol 40 (7) ◽  
pp. 101042831877648 ◽  
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Naoko Komura ◽  
Tadashi Kimura
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Gynecological Cancer ◽  
Suppressor Cells ◽  
Heterogeneous Population ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Activity ◽  
Anti Cancer ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells are a heterogeneous population of immature myeloid cells that exhibit immunosuppressive activity (they block the proliferation and activity of both T cells and natural killer cells). In addition to their role in suppressing immune responses, myeloid-derived suppressor cells directly stimulate tumor cell proliferation, metastasis, and angiogenesis. In the area of gynecological cancer, increased numbers of circulating myeloid-derived suppressor cells or tumor-infiltrating myeloid-derived suppressor cells have been detected, and the increased frequencies of myeloid-derived suppressor cells are associated with a poor prognosis. Thus, the successful myeloid-derived suppressor cells depletion may hold the key to maximizing existing anti-cancer therapies and improving the prognosis of gynecological cancer. In this review, we summarize current knowledge regarding myeloid-derived suppressor cells biology, clinical significance of myeloid-derived suppressor cells, and the potential myeloid-derived suppressor cells–targeting strategies in gynecological cancer.

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