Review of cancer cell resistance mechanisms to apoptosis and actual targeted therapies

2021 ◽  
Author(s):  
Merve Kulbay ◽  
Adeline Paimboeuf ◽  
Derman Ozdemir ◽  
Jacques Bernier
Keyword(s):  
Cancer Cell ◽  
Targeted Therapies ◽  
Resistance Mechanisms ◽  
Cell Resistance

Cancer cell resistance mechanisms: a mini review

2014 ◽  
Vol 16 (6) ◽  
pp. 511-516 ◽  
Author(s):  
S. Al-Dimassi ◽  
T. Abou-Antoun ◽  
M. El-Sibai
Keyword(s):  
Cancer Cell ◽  
Resistance Mechanisms ◽  
Cell Resistance

The role of hypoxia in endometrial cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Yarely M. Salinas-Vera ◽  
Dolores Gallardo-Rincón ◽  
Erika Ruíz-García ◽  
Macrina B. Silva-Cázares ◽  
Carmen Sol de la Peña-Cruz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Vasculogenic Mimicry ◽  
Cellular Processes ◽  
Corpus Uteri

: Endometrial cancer represents the most frequent neoplasia from the corpus uteri, and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance urged to ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors from breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

scholarly journals Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression

2011 ◽  
Vol 10 (1) ◽  
pp. 106 ◽  
Author(s):  
Uddalak Bharadwaj ◽  
Christian Marin-Muller ◽  
Min Li ◽  
Changyi Chen ◽  
Qizhi Yao
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cell Resistance ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals Understanding the Evolutionary Games in NSCLC Microenvironment

2020 ◽  
Author(s):  
Ranjini Bhattacharya ◽  
Robert Vander Velde ◽  
Viktoriya Marusyk ◽  
Bina Desai ◽  
Artem Kaznatcheev ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Targeted Therapies ◽  
Evolutionary Dynamics ◽  
Fusion Gene ◽  
Evolutionary Game ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Intrinsic Resistance ◽  
Frequency Changes

AbstractWhile initially highly successful, targeted therapies eventually fail as populations of tumor cells evolve mechanisms of resistance, leading to resumption of tumor growth. Historically, cell-intrinsic mutational changes have been the major focus of experimental and clinical studies to decipher origins of therapy resistance. While the importance of these mutational changes is undeniable, a growing body of evidence suggests that non-cell autonomous interactions between sub-populations of tumor cells, as well as with non-tumor cells within tumor microenvironment, might have a profound impact on both short term sensitivity of cancer cells to therapies, as well as on the evolutionary dynamics of emergent resistance. In contrast to well established tools to interrogate the functional impact of cell-intrinsic mutational changes, methodologies to understand non-cell autonomous interactions are largely lacking.Evolutionary Game Theory (EGT) is one of the main frameworks to understand the dynamics that drive frequency changes in interacting competing populations with different phenotypic strategies. However, despite a few notable exceptions, the use of EGT to understand evolutionary dynamics in the context of evolving tumors has been largely confined to theoretical studies. In order to apply EGT towards advancing our understanding of evolving tumor populations, we decided to focus on the context of the emergence of resistance to targeted therapies, directed against EML4-ALK fusion gene in lung cancers, as clinical responses to ALK inhibitors represent a poster child of limitations, posed by evolving resistance. To this end, we have examined competitive dynamics between differentially labelled therapy-naïve tumor cells, cells with cell-intrinsic resistance mechanisms, and cells with cell-extrinsic resistance, mediated by paracrine action of hepatocyte growth factor (HGF), within in vitro game assays in the presence or absence of front-line ALK inhibitor alectinib. We found that producers of HGF were the fittest in every pairwise game, while also supporting the proliferation of therapy-naïve cells. Both selective advantage of these producer cells and their impact on total population growth was a linearly increasing function of the initial frequency of producers until eventually reaching a plateau. Resistant cells did not significantly interact with the other two phenotypes. These results provide insights on reconciling selection driven emergence of subpopulations with cell non-cell autonomous resistance mechanisms, with lack of evidence of clonal dominance of these subpopulations. Further, our studies elucidate mechanisms for co-existence of multiple resistance strategies within evolving tumors. This manuscript serves as a technical report and will be followed up with a research paper in a different journal.

scholarly journals Thiourea and Guanidine Compounds and their Iridium Complexes in Drug-Resistant Cancer Cell Lines: Structure-Activity Relationships and Direct Luminescent Imaging

2019 ◽  
Author(s):  
Samuel J. Thomas ◽  
Barbora Balonova ◽  
Jindrich Cinatl ◽  
Mark Wass ◽  
Christopher Serpell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Nature Medicine ◽  
Cancer Cell Lines ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Iridium Complexes ◽  
Safety Issues ◽  
Structure Activity Relationships ◽  
Structure Activity

<p>Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. We have systematically synthesised a set of thiourea compounds and their guanidine analogues, and elucidated structure-activity relationships in terms of cellular toxicity in three ovarian cancer cell lines and their cisplatin-resistant sub-lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea- and guanidine-based materials.</p>

Expression of genes encoding NΑΔΗ−oxidase 5 and key antioxidant enzymes under formation of cancer cell resistance to cisplatin

2018 ◽  
Vol 120 ◽  
pp. S50
Author(s):  
Elena Kalinina ◽  
Yaroslav Andreev ◽  
Ksenia Lubova ◽  
Albina Petrova ◽  
Alexander Shtil ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Cancer Cell ◽  
Cell Resistance ◽  
Expression Of Genes ◽  
Genes Encoding

scholarly journals Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 407 ◽  
Author(s):  
Emily Hays ◽  
Benjamin Bonavida
Keyword(s):  
Nitric Oxide ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Tumor Regression ◽  
Cytotoxic T Cells ◽  
Resistance Mechanisms ◽  
Binding Activity ◽  
No Donors ◽  
Dna Binding Activity ◽  
Immune Resistance

In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression.

Sign in / Sign up

Export Citation Format

Share Document