P53 gene therapy. Oct 1, 2014 · Moreover, p53-based gene therapy could potentially overcome poor tumor responses to cytotoxic drugs: previous studies have shown that the simultaneous delivery of the wild-type p53 gene and doxorubicin using polymeric carriers can promote the inhibition of tumor growth and extend survival times [11], [12], [13], [14]. Gene therapy, compounds restoring WT conformation, HSP inhibitors, immunotherapy, and inhibition of synthetic lethal genes can be used for targeting cancer cells carrying mutant p53. During these years, most of the clinical trials and the relevant basic research Nov 6, 2020 · TP53 is the most frequently mutated tumor suppressor gene in human cancer. However, mutations in tumour suppressor genes are usually more associated to malignant diseases, with p53 being one of the most affected and studied element. The Oct 10, 2022 · With the introduction of newer, more sophisticated viral vectors, p53 gene therapy may hopefully become more effective and more broadly feasible, conceivably as part of combination therapy regimens 169. Dec 9, 2022 · One such gene that researchers have focused on for gene therapy of tumors is the p53 gene. Gendicine is a biolo … Apr 21, 2021 · In previous Ad-p53 gene therapy clinical trials in recurrent HNSCC, Ad-p53 was administered in treatment schedules of three times per week intratumorally either as three consecutive daily Ad-p53 treatments during the first week or every other day for the first 2 weeks of each monthly treatment cycle. , was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004. It consists of recombinant adenovirus engineered to code for p53 protein (rAd-p53) and is manufactured by Shenzhen SiBiono GeneTech. Three Aug 25, 2021 · The China Food and Drug Administration (CFDA) approved the first anti-tumor gene therapy drug rAd-p53 (recombinant human p53 adenovirus), Gendicine™. A phase I/II study was performed on 16 colorectal cancer patients with three intravenously injections of increasing dose of ALVAC encoding the human WT p53 gene (ALVAC-p53) at 3 week intervals (Menon et al. About Gene Therapy. 6). Ltd. Initially, mutations in TP53 were considered late events during malignant progression and associated with metastatic dissemination and castration resistance. [57] Certain pathogens can also affect the p53 protein that the TP53 gene expresses. Since p53 is largely restricted by MDM2/MDM4 through direct binding May 27, 2021 · Mutations in the tumor suppressor gene TP53 are among the most common genetic aberrations in cancer. Feb 9, 2022 · Loss of function in tumor suppressors is a driving force in tumorigenesis and the development of therapeutic resistance. Mutant p53 (Mutp53) proteins not only lose wild-type Oct 12, 2022 · Key Points: The p53 gene is mutated or deleted in approximately half of all cancers, and the p53 signaling pathway is disrupted in the remaining half. Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Jun 25, 2022 · Evaluation of p53 IHC. revealed that p53 transcriptionally activates NPAS2 to promote EMT of AT2 cells and BLM-mediated pulmonary fibrosis . The first of p53 gene replacement used a retroviral vector and showed that restoration of functional p53 suppressed the growth of some, but not all, human NSCLC cell lines in vitro. . Oct 10, 2022 · Presently, most p53-based immunotherapy clinical trials use a combination of immune checkpoint inhibition and a p53-activating agent (either gene therapy or small molecules). Oct 21, 2014 · Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary DNA copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). In prostate cancer, the role of mutant TP53 remains incompletely understood. About half of all human tumors harbor no TP53 mutations, but their WT p53 apparently fails to perform its tumor-suppressive job. It acts as a sensor of cellular homeostasis and plays important In a mouse model for NAFLD where p53 +/+ and p53-/-mice are fed a methionine- and choline-deficient diet, p53 +/+ mice show increases in histologically observable steatohepatitis, reactive oxygen species (ROS) formation, and fibrosis with increased protein levels of p66Shc, a protein associated with oxidative stress, as compared to p53-/-mice. The majority of mutations of p53 are missense mutations, leading to the expression of the full length p53 mutant proteins. As p53 function is lost in many cancers, it is logical to attempt restoring p53 function by reintroducing wt-p53 protein. Unlike viruses, nanoparticles have low immunogenicity and are thus Tumor suppressor p53 is the central component of a system maintaining the genetic stability of animal and human somatic cells. A successful p53 gene delivery system must meet several criteria. Despite major challenges associated with this approach, several Gene Therapy It is a state-of-the-art gene therapy aimed at blocking the infinite proliferation of cancer and destroying cancer cells. Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. However, recent studies report an inactivation of TP53 at an Mar 18, 2021 · Gene therapy aims to provide a functional gene copy of the damaged gene(s), increase the availability of disease-modifying genes or suppress the activity of a damaged gene. Gene Therapy It is a state-of-the-art gene therapy aimed at blocking the infinite proliferation of cancer and destroying cancer cells. 10–12 With this retroviral vector, intratumoral p53 gene therapy showed suppression of tumor growth in an orthotropic human NSCLC model with absent or mutant p53 Jan 15, 2018 · Here, we have investigated the potential of p53 gene therapy to augment immune checkpoint inhibition by combining an anti-programmed cell death protein 1 (PD1) antibody with SGT-53, our Oct 10, 2022 · With the introduction of newer, more sophisticated viral vectors, p53 gene therapy may hopefully become more effective and more broadly feasible, conceivably as part of combination therapy regimens 169. Other enhanced p53 gene therapies include creation of “super-p53,” in which the p53 tetramerization domain (TD) is replaced with alternative TD. Research and clinical trials are ongoing. Targeting p53 could be a successful treatment for mesothelioma or lung cancer. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. TP53 is located on the short arm of human chromosome 17 (17p13. Inactivation of p53 functions is an almost universal feature of human cancer cells. It’s often “the guardian of the genome” because of the important role it plays in preventing tumor development. ; Although research focused on designing effective therapies that target the p53 pathway has proven challenging, the different strategies of targeting p53 have shown varying efficacy in clinical trials to date. Jan 9, 2023 · Since p53 mutations are cancer-specific, several approaches targeting them have been taken to develop novel cancer therapies, including restoration or stabilization of wtp53 conformation from mutp53, rescue of p53 nonsense mutations, depletion of mutp53 proteins, and induction of p53 synthetic lethality or targeting of vulnerabilities imposed Dec 24, 2021 · Several studies have shown that transfection of cancer cells with wild-type p53 expressing plasmids can induce apoptosis and/or growth arrest, implying that a gene therapy method for cancer treatment could be based on restoring normal p53 expression and function. The p53-based gene therapy in oncology commonly aims to administer wild type-p53 or to suppress mutant p53 expression in p53-defective cancer cells [90,91]. p53 protein is a transcription factor that is usually divided into three functional domains: the amino-terminal domain, the DNA binding domain and the carboxy-terminal domain []. 271, 272, 273 Advances in adeno-associated virus (AAV) and nanoparticle techniques may enhance the development and application of p53 gene therapy. Mutation in the TP53 gene is detectable in about 50% of human breast, colon, lung, liver, prostate, bladder, and skin cancer. Upon DNA damage, wildtype p53 acts in restraining the process of cell replication until the damage is repaired, thus preventing the propagation of DNA-defective cells and the acquisition of a cancer phenotype (Fig. The P53 Tumor Suppressor Protein What is Cancer Gene Therapy? Cutting-edge treatment to work on "cancer" cause genes Cancer is the abnormal result of many Oct 25, 2023 · The TP53 gene is a gene that, when mutated, plays a large role in many cancers. Replication-defective adenoviruses are widely used as gene transfer vectors to deliver cytostatic or tumour suppressor genes into a variety of cancers, yielding some of the most promising results in the clinic. Jan 1, 2021 · p53-targeted cancer gene therapy. However, recent studies report an inactivation of TP53 at an Aug 1, 2021 · Strategies over the years have included of p53 gene therapy, stabilization of wild-type p53/degradation of mutant p53, restoration of mutant to wild-type p53 structural conformation, and small molecules that restore the p53 signaling pathway by activating downstream target of p53 even in p53-null cells (Fig. Oct 15, 2020 · In this study we undertook a novel combination therapy using rAd-p53 in situ gene therapy and immunotherapy with immune checkpoint inhibitor (ICI) anti-PD-1 antibody for urogenital cancers. This is a heavily studied pathway in cancer biology and oncology with a history that dates back to 1979 when p53 was discovered. The vector itself should be nontoxic and nonimmunogenic, allowing for multiple administrations if required. Background: Several gene deviations can be responsible for triggering oncogenic processes. This has spurred a tremendous effort to develop p53 based cancer therapies. The p53 tumor suppressor gene, a master regulator of cell cycle arrest Nov 18, 2022 · Mutp53 types in cancer. rAd-p53 infection into cells is a one-time event, and the viral debris that is present after the infection is unable to reproduce within the cells, and the adenoviral DNA is no longer able to combine into the host cell genome, so it is not genotoxic to humans. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. Oct 25, 2023 · The TP53 gene is a gene that, when mutated, plays a large role in many cancers. It delivers a functional copy of the p53 gene using an engineered adenovirus. Feb 27, 2023 · Over the years, gene therapy has advanced to multigene-based combination such as the combination of p53 and inhibitor of growth 4 (ING4), another tumor suppressor that enhances p53 acetylation and its transcriptional activity. Attempts to reactivate the gene have been challenging, but science has reached the point where early clinical trials are looking at drugs that may impact its function. The p53 gene is one of the most important of these tumor-suppressor genes. 8 This gene replacement therapy to transfer p53 gene directly into cancer cells has been demonstrated to suppress tumor growth because May 27, 2021 · Mutations in the tumor suppressor gene TP53 are among the most common genetic aberrations in cancer. Unlike viruses, nanoparticles have low immunogenicity and are thus Jan 25, 2022 · The tumor suppressor p53, also known as the guardian of the genome, is a transcription factor encoded by the TP53 gene in humans. The p53 gene codes a key protein responsible for regulating normal cell function. Suppression of mutant p53 function is proposed to be a robust approach to block the malignant development of CRC [41,92 Oct 7, 2022 · Another means of p53 reactivation as a gene therapy is direct introduction of functional wild-type p53 into cancer cells 168. , 2003). All Jul 17, 2024 · Tumor-based p53 therapies attempt to fix the mutated p53 gene and protein that causes cells to grow out of control, resulting in cancer in some people. Despite major challenges associated with this approach, several Dec 24, 2021 · p53 and cancer progression. Mar 1, 2023 · The p53 protein is a transcription factor that can activate the expression of multiple target genes and plays critical roles in regulating cell cycle, apoptosis, and genomic stability, and is Nov 18, 2022 · Numerous studies have found that interfering protein interactions, synergistic lethal therapies, gene therapy and genomic editing can also be used as therapeutic strategies for targeting mutp53 Sep 28, 2021 · As an important but highly mutated tumor-suppressive gene, p53 is an attractive therapeutic target for cancer therapy. Oct 3, 2008 · Cancer Gene Therapy. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial Gene therapy is a promising approach to restoring p53 function through delivery of the wild-type p53 gene to cancer cells. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. The p53-targeted therapy approach began with the identification of compounds capable of … Nov 16, 2021 · The first gene therapy product, recombinant adenovirus human p53 (rAd-p53), has been approved by CFDA since 2013. Furthermore, missense mutations are frequently transcribed and Dec 15, 2023 · p53, which is encoded by the most frequently mutated gene in cancer, TP53, is an attractive target for novel cancer therapies. p53 is implicated in a number of known cellular functions, including DNA damage repair, cell cycle arrest in G1/S and G2/M and apoptosis, being an Jul 2, 2024 · What Is p53 Gene Therapy? In human DNA, certain genes are responsible for preventing cells from becoming cancerous. Nov 3, 2021 · Gene therapy targeting p53 has been explored for various solid tumors. 8 This gene replacement therapy to transfer p53 gene directly into cancer cells has been demonstrated to suppress tumor growth because Nov 16, 2021 · The first gene therapy product, recombinant adenovirus human p53 (rAd-p53), has been approved by CFDA since 2013. Indeed, the most successful adenoviral vectors used to date are those that are designed to deliver p53 into tumours. [55] [56] The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. Overall p53 IHC staining quality was of sufficient standard to allow interpretation as wild-type or abnormal; although the blocks were from many different hospitals across Mar 28, 2024 · With gene therapy in disfavor, subsequent work on p53-based therapy took two main directions, instructed by the TP53 status of the treated cancer. Gene therapy using wild-type p53, delivered by adenovirus vectors, is now in widespread use in China. 6, 7 Gene therapy has a broad spectrum of applications, from gene replacement and knockdown for genetic disorders including cancer, hemophilia, hypercholesterolemia, and Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Dec 8, 2023 · This new gene therapy approach showed the ability to trigger apoptosis in cancer cell lines with various p53 mutations, indicating that it could be used as a therapy regardless of p53 status. Because of its almost universal inactivation in malignancy, p53 is a highly attractive t … Jan 29, 2024 · However, gene expression profiling of patient samples from these trials demonstrated that adenoviral p53 gene therapy treatment increased IFN signalling and was associated with a CD8 + T cell Mar 29, 2019 · We propose that p53 gene therapy and chemotherapy, when combined, will provide superior tumor cell killing for the treatment of prostate carcinoma. Nanoparticles have also been explored as p53 gene therapy vehicles (Fig. The p53 tumor suppressor gene, a master regulator of cell cycle arrest Oct 21, 2014 · Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary DNA copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). To this end, we have developed the AdRGD-PGp53 Sep 28, 2021 · TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. 1). May 9, 2024 · To treat p53-null tumors, one approach is to introduce p53 protein or use gene therapy to deliver p53 mRNA or DNA into tumor cells, thereby reinstating the expression of WT p53 protein. During these years, most of the clinical trials and the relevant basic research Oct 31, 2023 · Safety and efficacy of adenovirus-p53 gene therapy. Dec 15, 2023 · p53, which is encoded by the most frequently mutated gene in cancer, TP53, is an attractive target for novel cancer therapies. Adenovirus-based gene therapy, chemo and radiotherapy, MDM32 and MDMX inhibitors can be used to target cancer cells carrying wild type p53. 3). The P53 Tumor Suppressor Protein What is Cancer Gene Therapy? Cutting-edge treatment to work on "cancer" cause genes Cancer is the abnormal result of many May 14, 2024 · Neuronal PAS domain protein 2 (NPAS2) is a novel target gene of p53, Chen et al. Since the p53 gene is frequently inactivated by aberrant genetic regulation in human cancers, p53 replacement therapy is widely and frequently used as a potent antitumor strategy to restore wild-type p53 function in the p53-inactivated tumors. It was demonstrated for the first time in the late 1980s that transfection of the wt-p53 gene into a variety of human cancer cells could induce apoptosis and growth inhibition [37]. The p53 pathway is a complex cellular stress response network with … Jul 13, 2024 · Mutations in the TP53 tumor suppressor gene are highly prevalent in cancer; however, efforts to restore p53 functionality as a therapeutic strategy had limited success in late-stage clinical Nov 3, 2021 · The canarypox virus (ALVAC) is a well-characterized viral vector capable of infecting without replicating in mammalian cells. It has TP53 is the most commonly mutated gene in human cancer with over 100,000 literature citations in PubMed. 1) and consists of 11 exons, 10 introns and 393 amino acid residues. Reactivating the functions of tumor-suppressive factors is more challenging than directly inhibiting oncogenic factors. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. However, it was approved for treating head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy, and the data on its therapeutic potential in OS is not available. Its gene is inactivated in almost all human cancers, allowing a tumor cell to rapidly accumulate additional mutations and progress Gendicine is a gene therapy medication used to treat patients with head and neck squamous cell carcinoma linked to mutations in the TP53 gene. Targeting p53 is one focus of gene therapy research. Jul 1, 2024 · To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. hokqa ocdgue axjpvpsax vcqjuis jsr rfo pyhpli bqyyyo axm aqoe