Recent Progress in Gene Therapy for Ovarian Cancer

Ayén, Ángela; Martínez, Yaiza Jiménez; Marchal, Juan A.; Boulaiz, Houría

doi:10.3390/ijms19071930

Cited by 56 publications

(54 citation statements)

References 129 publications

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“…An overview of the treatment strategies developed for EOC over the past 30 years [27,28], from standard chemotherapy to anti-angiogenic therapy, and the latest incorporation of poly (ADP Ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, reveals that, although at a slower rate compared to other malignancies, increasing knowledge about genetic mutations and associated biological behavior are leading to the incorporation of the standard of care into the era of targeted therapy [8,29]. In this context, gene therapy, and in particular virotherapy [30], have explored different treatment opportunities and demonstrated encouraging preclinical results.…”

Section: Ovarian Cancermentioning

confidence: 99%

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

2020

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Ovarian cancer is the leading cause of death among women with gynecological cancer, with an overall 5-year survival rate below 50% due to a lack of specific symptoms, late stage at time of diagnosis and a high rate of recurrence after standard therapy. A better understanding of heterogeneity, genetic mutations, biological behavior and immunosuppression in the tumor microenvironment have allowed the development of more effective therapies based on anti-angiogenic treatments, PARP and immune checkpoint inhibitors, adoptive cell therapies and oncolytic vectors. Oncolytic adenoviruses are commonly used platforms in cancer gene therapy that selectively replicate in tumor cells and at the same time are able to stimulate the immune system. In addition, they can be genetically modified to enhance their potency and overcome physical and immunological barriers. In this review we highlight the challenges of adenovirus-based oncolytic therapies targeting ovarian cancer and outline recent advances to improve their potential in combination with immunotherapies.

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Section: Ovarian Cancermentioning

confidence: 99%

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

2020

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“…Cancer‐related genes of ovarian cancer include oncogenes, tumor suppressor genes, and DNA damage repair‐related genes . Proto‐oncogenes include EGFR, BRCA1‐/‐2, KRAS, PIK3CA, NOB1p , and other tumor suppressor genes, such as PTEN, TP53, P16 , and WWOX . Aiming at the pathogenesis of ovarian cancer, scientists have achieved significant breakthroughs in suppressing tumor growth by knocking out ovarian cancer oncogenes using CRISPR‐Cas9 technology (summarized in Table ).…”

Section: Ovarian Cancer and Crispr‐cas9mentioning

confidence: 99%

Applications of CRISPR‐Cas9 in gynecological cancer research

et al. 2020

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Gynecological cancers pose a significant threat to women's health worldwide, with cervical cancer, ovarian cancer, and endometrial cancer having high incidences.Current gynecological cancer treatment methods mainly include surgery, chemotherapy, radiotherapy, and chemoradiotherapy. The CRISPR-Cas9 gene editing technology as a new therapeutic method has shown tremendous effect in the treatment of other cancers, promoting research on its potential therapeutic effect in gynecological cancer. In this article, we reviewed the current research status of CRISPR-Cas9 technology in gynecological cancer, focusing on the importance of studying the mechanism of CRISPR-Cas9 in gynecological cancer treatment, thereby laying a foundation for further research on its clinical application. K E Y W O R D S cancer treatment, CRISPR-Cas9, gene editing, gynecological cancers 1 | INTRODUCTIONThe CRISPR sequence, a cluster of regularly spaced short palindromic repeats, is a special ordered repeating sequence found in the genome of Escherichia coli. The CRISPR-Cas9 system constitutes the acquired immune system of E. coli. 1 In 2012, scientists discovered that the CRISPR-Cas9 system can produce mature CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), which form a composite structure and have a directional guidance function to guide Cas9 to specific DNA sequences, resulting in DNA double-strand breaks. 2 By 2013, scientists had successfully edited the genome of eukaryotic cells using the CRISPR-Cas9 system. [3][4][5] Since then, the CRISPR-Cas9 gene editing technology has dramatically impacted the field of life sciences and has become one of the most significant research areas at present. The working principle of the CRISPR-Cas9 system is to artificially design two kinds of RNA: crRNA and tracrRNA, and then transform them into a single guide RNA (sgRNA), thereby guiding Cas9 to cut DNA in a targeted manner, following which cells are able to delete the target DNA through homologous and non-homologous DNA damage repair mechanisms. 6 Compared with traditional gene editing tools, such as ZFN and TALEN, the CRISPR-Cas9 technology has the advantages of simple design, ability to target any DNA sequence in the cell and to target multiple targets simultaneously, higher cutting efficiency, and lower cost. 7 At present, the CRISPR-Cas9 gene editing technology has contributed to great advancements in the clinical treatment of diseases. Major breakthroughs have been achieved in treating hereditary diseases using this technology. [8][9][10] It was used to knock out the beta-globin gene, the pathogenic gene of β-hemoglobinopathy, and it also employed rAAV6, as a donor template, to effectively correct the disease-causing mutation of SCD through homologous recombination. 10 In addition, The CRISPR-Cas9 gene editing technology has been widely used treatment-related researches and in the establishment of disease model of many cancers, including pancreatic, lung, gastric, colon, kidney, liver, head and neck, and skin cancers. [11][12][13][14][15][16][...

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“…Cisplatin (CP), carboplatin, paclitaxel (PTX), and docetaxel are common platinum‐based and taxane family drugs, respectively . Gene therapy is a promising area in ovarian cancer treatment . Much attention has been paid to enhancing agents that deliver genes for the treatment of this cancer .…”

Section: Introductionmentioning

confidence: 99%

“…20 Much attention has been paid to enhancing agents that deliver genes for the treatment of this cancer. 20 In addition, discovering novel agents for restoring downregulated genes, changing resistance to pharmacological drugs, and using suicide genes are other central points of investigations. 20 The application of nanotechnology is in both basic and translational medicine.…”

mentioning

confidence: 99%

“…20 In addition, discovering novel agents for restoring downregulated genes, changing resistance to pharmacological drugs, and using suicide genes are other central points of investigations. 20 The application of nanotechnology is in both basic and translational medicine. While chemotherapy drugs are very invasive and do not act specifically, the goal of nanomedicine is replacing them with agents that have the ability to function in the detection, diagnosis, imaging, and delivery of drugs to targets in a controlled manner.…”

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confidence: 99%

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Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

et al. 2019

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Although ovarian cancer has a lower prevalence than breast cancer, its mortality rate is three times higher, which is reported to increase in the coming years. As the early stages of ovarian cancer do not have any obvious symptoms, in most of the cases, this cancer is diagnosed at advanced stages with a poor prognosis. Moreover, in many patients who are diagnosed with advanced stage, relapse of the disease and drug resistance are observed. Over the past years, these women have been treated with chemotherapy and cytoreductive surgeries. However, the chemotherapy could affect the healthy tissues in addition to the malignancies. Therefore, discovering new diagnostic and therapeutic options seems to be a crucial need. Unlike the common invasive and/or nonspecific treatments, nanomedicine is trying to find a new way for cancer imaging, diagnosis, and drug delivery method. Nanoparticles (NPs), which has recently drawn attention, can be used in order to reduce the toxicity and frequent dosing of drugs, tumor‐specific delivery, and early diagnosis for malignancies. Chitosan as an NP and product of chitin deacetylation has multiple characteristics, including biocompatibility, biodegradability, and safety. In this review, we cover the studies concerned with the role of chitosan in finding solutions to overcome the problems faced in ovarian cancer treatments. Furthermore, we highlight how chitosan is being used in delivering chemotherapy drugs, gene therapy, and imaging methods for both detection and image‐guided therapies.

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Recent Progress in Gene Therapy for Ovarian Cancer

Cited by 56 publications

References 129 publications

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

Applications of CRISPR‐Cas9 in gynecological cancer research

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

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