Emerging Biological Treatments for Uterine Cervical Carcinoma

Vici, Patrizia; Mariani, Luciano; Pizzuti, Laura; Sergi, Domenico; Lauro, Luigi Di; Vizza, Enrico; Tomao, Federica; Tomao, Silverio; Mancini, Emanuela; Vincenzoni, Cristina; Barba, Maddalena; Maugeri-Saccá, Maugeri-Saccá Marcello; Giovinazzo, G.; Venuti, Aldo

doi:10.7150/jca.7963

Cited by 48 publications

(49 citation statements)

References 132 publications

(141 reference statements)

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“…Our results are similar to that of Bai et al [24] who indicated that ERK1/2 might promote the development of cervical cancer cells. We suggest that EGFR and ERK1/2 inhibitors might be used as an effective target for cervical cancer therapies This is in agreement with Vici et al [25] who declared that immunohistochemical expression level of molecular pathway targets might be of vital importance for deciding among therapeutic options.…”

Section: Discussionsupporting

confidence: 76%

Prognostic significance and therapeutic implications of PTEN, EGFR and MAPK/ERK in cervical squamous cell carcinoma

Mohammed¹,

Atwa²,

Hegazy³

et al. 2018

Am J Res Med Sci

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Introduction: There is a considerable need for cervical cancer treatments. The epidermal growth factor receptor (EGFR) and its pathway molecules affect cervical squamous cell carcinoma (CSCC) regarding its prognosis and anti-cancer therapy. Aims of Study:To investigate the biologic expression of EGFR and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway mediators in CSCCs, by investigating immunohistochemical expressions of EGFR, extracellular signalregulated kinases (ERK1/2) and phosphatase and tensin homolog (PTEN), in a trial to assess their prognostic and survival outcome. Patients and Methods: Immunohistochemical analysis was performed for 35 cervical squamous cell carcinoma specimens to detect three target antigens EGFR, PTEN, and MAPK/ERK1/2. Results: EGFR and MAPK/ERK1/2 staining showed a significant association with each of the following clinical parameters -increased patient age, high tumor stage, grade and positive lymph nodes (LN). They are also associated with relapse and poor patient survival. PTEN showed a significant association with decreased age, small tumor size, low grade, low stage and negative LN, meaning a good prognostic clinical outcome with less relapse. Conclusion: Cervical cancer patients with PTEN expression had good prognosis in contrary to those with EGFR and ERK expressions that had poor prognosis. Treatment directions of CSCC might be of great benefits in the form of an improved clinical outcome with EGFR pathway targeted therapy.

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Section: Discussionsupporting

confidence: 76%

Prognostic significance and therapeutic implications of PTEN, EGFR and MAPK/ERK in cervical squamous cell carcinoma

Mohammed¹,

Atwa²,

Hegazy³

et al. 2018

Am J Res Med Sci

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“…Researchers have observed promising preclinical activity with mapatumumab in patient with advanced solid cancers (Hotte et al, 2008). Currently, mapatumumab in combination with bortezomib in patients with refractory myeloma (Kapoor et al, 2012) and cisplatin and radiotherapyin patients with cervical cancer is in phase II clinical trials (Vici et al, 2014).…”

Section: Targeting the Extrinsic Pathwaymentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

462

338

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Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

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“…Current strategies for treating HPV cancers have been only moderately successful and characterized by recurrence. 1 The available preventive vaccination (Gardasil, Gardasil-9 and Cervarix, based on the recombinant major capsid viral protein L1 of variously incident HPVs) will probably reduce the number of HPV cancer cases and of precancerous lesions worldwide, resulting in lives saved and related morbidity and cost-offsets. 2 Nevertheless, these benefits will be visible in the next decades and, without a profound shift in rates of vaccination in men and women worldwide, prophylactic vaccination will not have great impact at least on the incidence of certain HPV infections like those causing oropharyngeal cancers, that are currently in a dramatic rise.…”

Section: Introductionmentioning

confidence: 99%

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

Massa

Paolini²,

Curzio³

et al. 2017

Human Vaccines & Immunotherapeutics

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Signal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a proper immunological response. Thus, a plant ss was used to drive Human Papillomavirus (HPV) model antigens into the human secretory pathway: the HPV16 E7 oncoprotein, its chimera with the coat protein (CP) of the Potato Virus X (PVX), the first 200 amino acids of the HPV16 minor capsid protein L2 (known to harbour cross-reacting epitopes) and its chimera with E7 gene. These genes were used to transfect HEK-293 cells and to immunize C57BL/6 mice. The ss-provided genes were expressed, and proteins detected by immunofluorescence and immunoblotting. Mouse immunization with DNA constructs carrying the ss elicited a strong humoral response against both E7 and L2 and a weak cell-mediated immunity.To our knowledge this is the first demonstration that a signal sequence derived from a plant can modulate the sorting of a heterologous protein in mammalian cells. This activity in mammalian cells may be responsible for the observed increased humoral response to DNA-based vaccines that are generally weak inducers of IgG response. This might open new perspectives in the design of DNA vaccines, especially to counteract infections where a strong humoral response is needed.

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Emerging Biological Treatments for Uterine Cervical Carcinoma

Cited by 48 publications

References 132 publications

Prognostic significance and therapeutic implications of PTEN, EGFR and MAPK/ERK in cervical squamous cell carcinoma

Prognostic significance and therapeutic implications of PTEN, EGFR and MAPK/ERK in cervical squamous cell carcinoma

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

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