Molecular targeted therapy: Treating cancer with specificity

Lee, Yeuan Ting; Tan, Yi; Oon, Chern Ein

doi:10.1016/j.ejphar.2018.07.034

Cited by 793 publications

(500 citation statements)

References 76 publications

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“…Clinicians have also found that because of the wide variety of human tumors and even in tumors at the same tumor site, the treatment effect and methods are not the same. Therefore, in the course of cancer treatment, only individualized treatment can be implemented to select the right medicine for different types of patients . Currently, molecular detection has brought about widespread changes in cancer treatment models, and gene therapy has also built a new world in the direction of targeted therapy .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Therefore, in the course of cancer treatment, only individualized treatment can be implemented to select the right medicine for different types of patients. 106 Currently, molecular detection has brought about widespread changes in cancer treatment models, and gene therapy has also built a new world in the direction of targeted therapy. 107,108 Clinically, potential therapeutic targets can be discovered by detecting the amplification/mutation/expression of specific genes in related pathways, and a suitable treatment plan can be tailored for each patient.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Sun

Yan

2019

Clinical Genetics

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Cancer is a common type of non-communicable disease, and its morbidity and mortality are rapidly increasing. It is expected to become the largest obstacle to the promotion of global human health in the future. Some transcription factors that play important regulatory roles in embryogenesis and subsequent tissue maintenance can be selectively amplified during tumorigenesis. Due to its high expression in the embryonic endoderm and mesoderm, GATA6 plays a crucial role in the normal development of early human heart, lung, digestive system, adrenal glands, breasts, ovaries, retina, skin, and nervous system. Up to now, overexpression of the GATA6 gene has been shown to play an important role in several cancers, including lung cancer, digestive system tumors, breast cancer, and ovarian cancer. However, the human body is a complex organism, which causes the transcription factor GATA6 to have multiple roles in cancer. In this review, we summarize the multiple roles of transcription factor GATA6 in various cancers and its regulatory mechanisms. The aim is to better understand the relationship between GATA6 gene expression and cancer development and to provide new insights for exploring potential therapeutic targets.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Sun

Yan

2019

Clinical Genetics

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“…In order to reduce the mortality rate of breast cancer, molecular-targeted therapy is emerging as an alternative treatment (5). In previous decades, efforts have been concentrated on the discovery of molecular targets; numerous molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of breast cancer (6). However, breast cancer associated incidence and mortality has been steadily increasing from 2000 through to 2011 (7,8).…”

Section: Introductionmentioning

confidence: 99%

The effect of centromere protein U silencing by lentiviral mediated RNA interference on the proliferation and apoptosis of breast cancer

Lin

Mao

et al. 2018

Oncol Lett

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Centromere protein U (CENPU) is a novel transcriptional repressor that is associated with different types of cancer. However, its function in breast cancer is poorly understood. In the present study, it was identified that CENPU was highly expressed in breast cancer tissues compared with expression in normal breast tissues (P=0.001). Furthermore, the CENPU mRNA level in tumors was often elevated, compared with the matched adjacent normal breast cancer tissue specimens in the dataset from The Cancer Genome Atlas database (n=106; P<0.001). To understand the function of CENPU in human breast carcinogenesis, its effects on the proliferation, apoptosis and cell cycle progression of MDA-MB-231 cells were examined using the lentiviral-mediated CENPU knockdown approach. The RNA and protein expression levels in the transfected cells were monitored using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The mRNA and protein expression levels of the CENPU gene were significantly lower in the CENPU-shRNA transfected cells than in the control (P<0.01), indicating successful gene expression knockdown. Post-transfection, cell counting and MTT analysis revealed that the proliferation activity was significantly suppressed in CENPU knockdown cells relative to the control (P<0.01). Additionally, fluorescence activated cell sorting analysis revealed that the (G2+S) phase fraction was significantly declined in CENPU knockdown cells relative to the control; while the G1 phase fraction was significantly increased (P<0.01) and the percentage of the apoptotic cells was significantly increased (P<0.01). In conclusion, downregulation of CENPU gene expression may inhibit cell proliferation and cell cycle progression, and increase the apoptosis of the breast cancer cells. These results suggested a possible function of this protein in breast cancer pathogenesis and prognosis.

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“…Large-scale cancer sequencing initiatives have opened up a window into the genome of 2 individual cancers, offering unprecedented opportunities for studying the functional 3 consequences of molecular alterations in human cancers [1]. However, despite new 4 evidence highlighting the importance of cancer-specific splice variants in tumor 5 initiation and progression, the role played by splice variants in the biology of human 6 cancers and patient survival is still poorly understood.…”

mentioning

confidence: 99%

“…The general strategy 20 in targeted therapy is to use small molecules to inhibit specific pathways important for 21 cancer cell survival and invasiveness. [3]. However, for molecular targeted therapy to be 22 successful, it is important to identify highly specific molecular mechanisms that lead to 23 tumor survival and metastasis.…”

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confidence: 99%

Uncovering and characterizing splice variants associated with survival in lung cancer patients

West

Kumar

Batra

et al. 2019

Preprint

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Splice variants have been shown to play an important role in tumor initiation and progression and can serve as novel cancer biomarkers. However, the clinical importance of individual splice variants and the mechanisms by which they can perturb cellular functions are still poorly understood. To address these issues, we developed an efficient and robust computational method to: (1) identify splice variants that are associated with patient survival in a statistically significant manner; and (2) predict rewired protein-protein interactions that may result from altered patterns of expression of such variants. We applied our method to the lung adenocarcinoma dataset from TCGA and identified splice variants that are significantly associated with patient survival and can alter protein-protein interactions. Among these variants, several are implicated in DNA repair through homologous recombination. To computationally validate our findings, we characterized the mutational signatures in patients, grouped by low and high expression of a splice variant associated with patient survival and involved in DNA repair. The results of the mutational signature analysis are in agreement with the molecular mechanism suggested by our method. To the best of our knowledge, this is the first attempt to build a computational approach to systematically identify splice variants associated with patient survival that can also generate experimentally testable, mechanistic hypotheses. Code for identifying survival-significant splice variants using the Null Empirically Estimated P-value method can be found at https://github.com/thecodingdoc/neep. Code for construction of Multi-Granularity Graphs to discover potential rewired protein interactions can be found at https://github.com/scwest/SINBAD. Presentation slides are found at https://github.com/scwest/RECOMB-CBB 2019 NEEP. Author summaryIn spite of many recent breakthroughs, there is still a pressing need for better ways to diagnose and treat cancer in ways that are specific to the unique biology of the disease. Novel computational methods applied to large-scale datasets can help us reach this goal more effectively. In this work we shed light on a still poorly understood biological process that is often aberrant in cancer and that can lead to tumor formation, progression, and invasion. This mechanism is alternative splicing and is the ability of one gene to code for many different variants with distinct functions. We developed a fast and statistically robust approach to identify splice variants that are significantly May 3, 2019 1/16 associated with patient survival. Then, we computationally characterized the protein products of these splice variants by identifying potential losses and gains of protein interactions that could explain their biological role in cancer. We applied our method to a lung adenocarcinoma dataset and identified several splice variants associated with patient survival that lose biologically important interactions. We conducted case studies and computationally validated some ...

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Molecular targeted therapy: Treating cancer with specificity

Cited by 793 publications

References 76 publications

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

The effect of centromere protein U silencing by lentiviral mediated RNA interference on the proliferation and apoptosis of breast cancer

Uncovering and characterizing splice variants associated with survival in lung cancer patients

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