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Cancers
Special Issues
Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis
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Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 29610

Special Issue Editor

Prof. Dr. Katrien Remaut

E-Mail Website
Guest Editor
Lab General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
Interests: peritoneal carcinomatosis; advanced microscopy methods; nucleic acid delivery; non-viral gene delivery; stability in biological fluids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Cancer, including breast cancer, skin cancer, lung cancer, colon cancer and prostate cancer still affects millions of people every year. Cancer treatment often includes non-specific interventions such as surgery, chemotherapy and/or radiation therapy. Targeted therapies, however, specifically interfere with the biology of the cancer cells, to prevent the growth and formation of metastasis. Biological therapies such as immunotherapy, antibodies, gene therapy and cell-based therapy are also rapidly progressing. Furthermore, smart delivery strategies such as tumor-environment responsive materials, controlled-release formulations or the application of local triggers (light, heat, ultrasound, etc.) can locally boost the therapeutic potential.

In this Special Issue, we will publish reviews and original research that provide new insights into gene targeted therapies for cancer metastasis and how locoregional treatment can advance the therapeutic outcomes. Novel insights into the delivery aspects of gene targeted therapies will be particularly welcomed.

Prof. Dr. Katrien Remaut
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nucleic acids in cancer treatment (siRNA, mRNA, pDNA, …)
  • antibodies in cancer treatment
  • immunotherapy
  • cancer vaccines
  • cancer gene therapy
  • cell based therapy
  • mesenchymal to epithelial cell transition
  • tumor environment responsive materials
  • controlled release formulations
  • locoregional triggered drug delivery
  • delivery barriers to targeted cancer therapies

Published Papers (5 papers)

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Research

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27 pages, 3523 KiB  
Article
Deciphering the Molecular Basis of Melatonin Protective Effects on Breast Cells Treated with Doxorubicin: TWIST1 a Transcription Factor Involved in EMT and Metastasis, a Novel Target of Melatonin
by Javier Menéndez-Menéndez, Francisco Hermida-Prado, Rocío Granda-Díaz, Alicia González, Juana María García-Pedrero, Nagore Del-Río-Ibisate, Alicia González-González, Samuel Cos, Carolina Alonso-González and Carlos Martínez-Campa
Cancers 2019, 11(7), 1011; https://doi.org/10.3390/cancers11071011 - 19 Jul 2019
Cited by 33 | Viewed by 5594
Abstract
Melatonin mitigates cancer initiation, progression and metastasis through inhibition of both the synthesis of estrogens and the transcriptional activity of the estradiol-ER (Estrogen receptor) complex in the estrogen-dependent breast cancer cell line MCF-7. Moreover, melatonin improves the sensitivity of MCF-7 to chemotherapeutic agents [...] Read more.
Melatonin mitigates cancer initiation, progression and metastasis through inhibition of both the synthesis of estrogens and the transcriptional activity of the estradiol-ER (Estrogen receptor) complex in the estrogen-dependent breast cancer cell line MCF-7. Moreover, melatonin improves the sensitivity of MCF-7 to chemotherapeutic agents and protects against their side effects. It has been described that melatonin potentiates the anti-proliferative effects of doxorubicin; however, the molecular changes involving gene expression and the activation/inhibition of intracellular signaling pathways remain largely unknown. Here we found that melatonin enhanced the anti-proliferative effect of doxorubicin in MCF-7 but not in MDA-MB-231 cells. Strikingly, doxorubicin treatment induced cell migration and invasion, and melatonin effectively counteracted these effects in MCF-7 but not in estrogen-independent MDA-MB-231 cells. Importantly, we describe for the first time the ability of melatonin to downregulate TWIST1 (Twist-related protein 1) in estrogen-dependent but not in estrogen-independent breast cancer cells. Combined with doxorubicin, melatonin inhibited the activation of p70S6K and modulated the expression of breast cancer, angiogenesis and clock genes. Moreover, melatonin regulates the levels of TWIST1-related microRNAs, such as miR-10a, miR-10b and miR-34a. Since TWIST1 plays a pivotal role in the epithelial to mesenchymal transition, acquisition of metastatic phenotype and angiogenesis, our results suggest that inhibition of TWIST1 by melatonin might be a crucial mechanism of overcoming resistance and improving the oncostatic potential of doxorubicin in estrogen-dependent breast cancer cells. Full article
(This article belongs to the Special Issue Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis)
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17 pages, 28508 KiB  
Article
Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts
by Holly A. Maulhardt, Lauren Hylle, Michael V. Frost, Ashley Tornio, Sara Dafoe, Leanne Drummond, David I. Quinn, Ashish M. Kamat and Gere S. diZerega
Cancers 2019, 11(4), 577; https://doi.org/10.3390/cancers11040577 - 24 Apr 2019
Cited by 13 | Viewed by 3518
Abstract
Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce®, NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce®, IV-docetaxel and IT-vehicle were administered to [...] Read more.
Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce®, NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce®, IV-docetaxel and IT-vehicle were administered to clear cell renal carcinoma (786-O: rats), transitional cell bladder carcinoma (UM-UC-3: mice) and prostate carcinoma (PC-3: mice). Treatments were given every 7 days with 1, 2, or 3 doses administered. Animals were followed for tumor growth and clinical signs. At necropsy, 786-O and UM-UC-3 tumor-site tissues were evaluated by H&E and IHC and analyzed by LC-MS/MS for docetaxel concentration. Two and 3 cycles of IT-NanoDoce® significantly reduced UM-UC-3 tumor volume (p < 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce® treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce®-treated UM-UC-3 animals adjacent to tumor sites. IT-vehicle and IV-docetaxel exhibited limited immune-cell infiltration. In both studies, high levels of docetaxel were detected in NanoDoce®-treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce® and IV-docetaxel resulted in similar tumor reduction. NanoDoce® significantly reduced tumor volume compared to IT-vehicle in all xenografts (p < 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce® reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce® treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects. Full article
(This article belongs to the Special Issue Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis)
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21 pages, 6886 KiB  
Article
Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo
by Yusuf A. Haggag, Kyle B. Matchett, Robert A. Falconer, Mohammad Isreb, Jason Jones, Ahmed Faheem, Paul McCarron and Mohamed El-Tanani
Cancers 2019, 11(2), 222; https://doi.org/10.3390/cancers11020222 - 14 Feb 2019
Cited by 28 | Viewed by 4709
Abstract
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and [...] Read more.
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs). A modified double emulsion solvent evaporation technique was used to optimise the physicochemical properties of these peptide-loaded biodegradable NPs. The anti-cancer activity of peptide-loaded NPs was studied in vitro using Ran-expressing metastatic breast (MDA-MB-231) and lung cancer (A549) cell lines, and in vivo using Solid Ehrlich Carcinoma-bearing mice. The anti-metastatic activity of peptide-loaded NPs was investigated using migration, invasion and colony formation assays in vitro. A PEG-PLGA-nanoparticle encapsulating N-terminal peptide showed a pronounced antitumor and anti-metastatic action in lung and breast cancer cells in vitro and caused a significant reduction of tumor volume and associated tumor growth inhibition of breast cancer model in vivo. These findings suggest that the novel inhibitory peptides encapsulated into PEGylated PLGA NPs are delivered effectively to interact and deactivate Ran. This novel Ran-targeting peptide construct shows significant potential for therapy of breast cancer and other cancers mediated by Ran overexpression. Full article
(This article belongs to the Special Issue Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis)
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Review

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20 pages, 1691 KiB  
Review
Aerosolization of Nanotherapeutics as a Newly Emerging Treatment Regimen for Peritoneal Carcinomatosis
by Molood Shariati, Wouter Willaert, Wim Ceelen, Stefaan C. De Smedt and Katrien Remaut
Cancers 2019, 11(7), 906; https://doi.org/10.3390/cancers11070906 - 28 Jun 2019
Cited by 16 | Viewed by 6301
Abstract
Recent advances in locoregional chemotherapy have opened the door to new approaches for the clinical management of peritoneal carcinomatosis (PC) by facilitating the delivery of anti-neoplastic agents directly to the tumor site, while mitigating adverse effects typically associated with systemic administration. In particular, [...] Read more.
Recent advances in locoregional chemotherapy have opened the door to new approaches for the clinical management of peritoneal carcinomatosis (PC) by facilitating the delivery of anti-neoplastic agents directly to the tumor site, while mitigating adverse effects typically associated with systemic administration. In particular, an innovative intra-abdominal chemotherapeutic approach, known as Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), was recently introduced to the intraperitoneal (IP) therapy regimens as a palliative therapeutic option in patients with PC, presumably providing a better drug distribution pattern together with deeper drug penetration into tumor nodules within the peritoneal space. Furthermore, the progress of nanotechnology in the past few decades has prompted the application of different nanomaterials in IP cancer therapy, offering new possibilities in this field ranging from an extended retention time to sustained drug release in the peritoneal cavity. This review highlights the progress, challenges, and opportunities in utilizing cancer nanotherapeutics for locoregional drug delivery, with a special emphasis on the aerosolization approach for intraperitoneal therapies. Full article
(This article belongs to the Special Issue Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis)
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22 pages, 987 KiB  
Review
The Role of Epithelial-to-Mesenchymal Plasticity in Ovarian Cancer Progression and Therapy Resistance
by Nele Loret, Hannelore Denys, Philippe Tummers and Geert Berx
Cancers 2019, 11(6), 838; https://doi.org/10.3390/cancers11060838 - 17 Jun 2019
Cited by 160 | Viewed by 8778
Abstract
Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent [...] Read more.
Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent development of resistance to current chemotherapeutic regimens. Growing evidence demonstrates that apart from its role in ovarian cancer progression, epithelial-to-mesenchymal transition (EMT) can promote chemotherapy resistance. In this review, we will highlight the contribution of EMT to the distinct steps of ovarian cancer progression. In addition, we will review the different types of ovarian cancer resistance to therapy with particular attention to EMT-mediated mechanisms such as cell fate transitions, enhancement of cancer cell survival, and upregulation of genes related to drug resistance. Preclinical studies of anti-EMT therapies have yielded promising results. However, before anti-EMT therapies can be effectively implemented in clinical trials, more research is needed to elucidate the mechanisms leading to EMT-induced therapy resistance. Full article
(This article belongs to the Special Issue Locoregional Treatment and Gene Targeted Therapies for Cancer Metastasis)
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