Concise Review: Cancer Cells Escape from Oncogene Addiction: Understanding the Mechanisms Behind Treatment Failure for More Effective Targeting

Stem Cells ◽  
2014 ◽  
Vol 32 (6) ◽  
pp. 1373-1379 ◽  
Author(s):  
Francesca Pellicano ◽  
Leena Mukherjee ◽  
Tessa L. Holyoake
Keyword(s):  
Treatment Failure ◽  
Cancer Cells ◽  
Oncogene Addiction ◽  
Concise Review

scholarly journals Non-Oncogene Addiction and the Stress Phenotype of Cancer Cells

Cell ◽  
2007 ◽  
Vol 130 (6) ◽  
pp. 986-988 ◽  
Author(s):  
Nicole L. Solimini ◽  
Ji Luo ◽  
Stephen J. Elledge
Keyword(s):  
Cancer Cells ◽  
Oncogene Addiction

scholarly journals Pan-cancer analysis of non-oncogene addiction to DNA repair

2021 ◽  
Author(s):  
Luis Bermúdez-Guzmán
Keyword(s):  
Overall Survival ◽  
Dna Repair ◽  
Cancer Cells ◽  
Synthetic Lethality ◽  
The Cancer Genome Atlas ◽  
Molecular Signature ◽  
Systematic Evaluation ◽  
Oncogene Addiction ◽  
Poor Overall Survival ◽  
Pan Cancer

Abstract Cancer cells usually depend on the aberrant function of one or few driver genes to initiate and promote their malignancy, an attribute known as oncogene addiction. However, cancer cells might become dependent on the normal cellular functions of certain genes that are not oncogenes but ensure cell survival (non-oncogene addiction). The downregulation of DNA repair genes and the consequent genetic and epigenetic instability is key to promote malignancy, but the activation of the DNA-damage response (DDR) has been shown to become a type of non-oncogene addiction that critically supports tumour survival. While we know that different cancer types can become dependent on specific DDR genes for their survival, a systematic evaluation of DNA repair addiction at the pan-cancer level is missing. In the present study, this systematic evaluation was addressed using data derived from The Cancer Dependency Map and The Cancer Genome Atlas (TCGA). Following this approach, 59 DDR genes were identified as commonly essential in cancer cells with 14 genes being exclusively associated with better overall patient survival and 19 with worse overall survival. Notably, a specific molecular signature among the latter, characterized by DDR genes showing the weakest dependency scores, but significant upregulation was strongly associated with worse survival, supporting the presence and relevance of non-oncogenic addiction to DNA repair in cancer. Particularly, UBE2T, RFC4, POLQ, BRIP1, and H2AFX represent the best predictors of poor overall survival, and some might represent promising therapeutic targets, especially under the synthetic lethality approach.

scholarly journals Concise review: The role of cancer-derived exosomes in tumorigenesis and immune cell modulation

2020 ◽  
Vol 7 (12) ◽  
pp. 4158-4169
Author(s):  
Nhi Thao Huynh ◽  
Khuong Duy Pham ◽  
Nhat Chau Truong
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Vascular System ◽  
Immune Surveillance ◽  
Cell Communication ◽  
Tumor Formation ◽  
Concise Review ◽  
The Relationship

Exosomes are subcellular entities which were first discovered in the 1980s. Over the past decade, scientists have discovered that they carry components of genetic information that allow for cell-cell communication and cell targeting. Exosomes secreted by cancer cells are termed cancer-derived exosomes (CDEs), and play an important role in tumor formation and progression. Specifically, CDEs mediate the communication between cancer cells, as well as between cancer cells and other cells in the tumor microenvironment, including cancer-associated fibroblasts, endothelial cells, mesenchymal stem cells, and effector immune cells. Additionally, through the vascular system and body fluids, CDEs can modulate response to drugs, increase angiogenesis, stimulate proliferation, promote invasion and metastasis, and facilitate escape from immune surveillance. This review will discuss the relationship between cancer cells and other cells (particularly immune cells), as mediated through CDEs, as well as the subsequent impact on tumorigenesis and immunomodulation. Understanding the role of CDEs in tumorigenesis and immune cell modulation will help advance their utilization in the diagnosis, prognosis, and treatment of cancer.

The roles of radio-functional natural chemicals for the development of cancer radiation therapy

2019 ◽  
Vol 34 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Lei Jiang ◽  
Hitoshi Iwahashi
Keyword(s):  
Oxidative Stress ◽  
Radiation Therapy ◽  
Side Effects ◽  
Treatment Failure ◽  
Cancer Cells ◽  
Review Article ◽  
Antioxidant Ability ◽  
Acute Side Effects ◽  
Normal Human ◽  
Low Toxicity

Abstract Ionizing radiation (IR) targeted at killing cancer cells also damages normal human cells and tissues through oxidative stress. Thus, the practical treatment of cancer using radiation therapy (RT) is sometimes limited because of the acute side effects in individual patients. In addition, some radioresistant cancers are difficult to treat with limited doses of IR, which leads to treatment failure. Natural chemicals that have unique physiological functions and low toxicity offer significant advantages for the development of new radiation therapies. Natural chemicals can counteract the oxidative damage caused by IR during RT because of their strong antioxidant ability. Certain natural chemicals can also serve as radiosensitizers that can enhance the cancer-killing effects. This review article discusses the main roles of radio-functional natural chemicals in the development of cancer RT.

Repopulation of cancer cells during therapy: an important cause of treatment failure

2005 ◽  
Vol 5 (7) ◽  
pp. 516-525 ◽  
Author(s):  
John J. Kim ◽  
Ian F. Tannock
Keyword(s):  
Treatment Failure ◽  
Cancer Cells

scholarly journals Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction

2020 ◽  
Author(s):  
Reina E. Ito ◽  
Chitose Oneyama ◽  
Kazuhiro Aoki
Keyword(s):  
Cancer Cells ◽  
Mammary Epithelium ◽  
Oncogene Addiction ◽  
Oncogenic Mutation ◽  
Tumorigenic Potential ◽  
Human Mammary Epithelium ◽  
Single Allele ◽  
Tumorigenic Activity ◽  
Cellular Property ◽  
Synthetic Biology Approach

AbstractOncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak tumorigenic activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the tumorigenic activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cancer cells to acquire oncogene addiction, and that oncogene addiction is not associated with tumorigenic potential.

scholarly journals Pan-cancer analysis of non-oncogene addiction to DNA repair

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luis Bermúdez-Guzmán
Keyword(s):  
Dna Repair ◽  
Cancer Cells ◽  
Cell Lines ◽  
The Cancer Genome Atlas ◽  
Molecular Signature ◽  
Systematic Evaluation ◽  
Oncogene Addiction ◽  
Driver Genes ◽  
Using Data ◽  
Pan Cancer

AbstractCancer cells usually depend on the aberrant function of one or few driver genes to initiate and promote their malignancy, an attribute known as oncogene addiction. However, cancer cells might become dependent on the normal cellular functions of certain genes that are not oncogenes but ensure cell survival (non-oncogene addiction). The downregulation or silencing of DNA repair genes and the consequent genetic and epigenetic instability is key to promote malignancy, but the activation of the DNA-damage response (DDR) has been shown to become a type of non-oncogene addiction that critically supports tumour survival. In the present study, a systematic evaluation of DNA repair addiction at the pan-cancer level was performed using data derived from The Cancer Dependency Map and The Cancer Genome Atlas (TCGA). From 241 DDR genes, 59 were identified as commonly essential in cancer cell lines. However, large differences were observed in terms of dependency scores in 423 cell lines and transcriptomic alterations across 18 cancer types. Among these 59 commonly essential genes, 14 genes were exclusively associated with better overall patient survival and 19 with worse overall survival. Notably, a specific molecular signature among the latter, characterized by DDR genes like UBE2T, RFC4, POLQ, BRIP1, and H2AFX showing the weakest dependency scores, but significant upregulation was strongly associated with worse survival. The present study supports the existence and importance of non-oncogenic addiction to DNA repair in cancer and may facilitate the identification of prognostic biomarkers and therapeutic opportunities.

scholarly journals The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 240 ◽  
Author(s):  
Phung Huong ◽  
Lap Nguyen ◽  
Xuan-Bac Nguyen ◽  
Sang Lee ◽  
Duc-Hiep Bach
Keyword(s):  
Drug Resistance ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Treatment Failure ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapeutic Drugs ◽  
Activated Platelets

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet–cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

scholarly journals Targeting Oncogene Addiction for Cancer Therapy

2021 ◽  
Author(s):  
Sonia Thapa ◽  
Rafiq A. Rather ◽  
Shashank K. Singh ◽  
Madhulika Bhagat
Keyword(s):  
Cancer Cells ◽  
Mammalian Cell Culture ◽  
Genetic Alterations ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Oncogene Addiction ◽  
Critical Pathway ◽  
Culture Models ◽  
Intervention Trials ◽  
Novel Therapeutic Strategies

Oncogene addiction, a term first coined by Bernard Weinstein in 2000, refers to a condition where a tumor cell, despite harboring a multitude of genetic alterations, depends on a single oncogenic pathway or oncoprotein for sustained proliferation and survival. Several lines of evidence from mammalian cell culture models, genetically modified mice models, and human intervention trials of targeted drugs have revealed that many tumors, if not all, rely on oncogene addiction for sustained proliferation and survival. Oncogene addiction strongly impacts the therapeutic response of tumors to acute oncoprotein inhibition. An important implication of oncogene addiction is that inhibiting this critical pathway, on which cancer cells become dependent, can cause selective and specific cell death in cancer cells while sparing normal surrounding cells that are not oncogene addicted. However, the mechanism by which cancer cells become dependent on a single pathway or activated oncoprotein is not precisely understood in most cases. Thus, a better understanding of oncogene addiction may provide a rationale for improving current cancer therapies and help develop novel therapeutic strategies for the management of cancer.

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