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Life
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New Therapeutic Strategies in Pancreatic Cancer
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New Therapeutic Strategies in Pancreatic Cancer

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 14382

Special Issue Editor

Dr. Graziana Digiacomo

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Interests: cell culture; oncology; molecular and cell biology; signaling pathways; hepatocarcinoma; lung cancer; CDK4/6-inhibitors; macrophages; angiogenesis; cell migration and invasion; target therapy; western blot analysis; gene expression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pancreatic cancer is currently the third leading cause of cancer-related death and is estimated to become the second leading cause within the next decade. Pancreatic cancer remains the most lethal human cancer, having a five-year survival rate of only about 10%. The current treatment for patients for both local and metastatic disease is a combination of chemotherapeutic agents. FOLFIRINOX and the combination of gemcitabine with nab-paclitaxel remain the primary first-line treatment options. Pancreatic cancer presents frequent alterations in oncogenes or tumor suppressor genes such as KRAS, TP53, SMAD4, and CDKN2A. Further studies to test novel agents that specifically target these altered signaling pathways will be critical for the design of new therapeutic strategies. These novel agents will probably need to be used as part of combination approaches with a standard chemotherapeutic regimen or with an immunotherapy approach to prevent early resistance mechanisms from emerging. These new advances should achieve considerable survival benefits with reduced side effects and mortality of patients with pancreatic cancer.

This Special Issue aims to publish original research or reviews concerning the treatment options for pancreatic cancers, highlighting new advances in this field.

Dr. Graziana Digiacomo
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. Life is an international peer-reviewed open access monthly 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 2600 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

  • pancreatic cancer
  • tumor biology
  • molecular markers
  • drug combination
  • target therapy
  • immunotherapy
  • KRAS
  • CDKN2A

Published Papers (5 papers)

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Research

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12 pages, 2600 KiB  
Article
It Takes Two to Tango: Potential Prognostic Impact of Circulating TGF-Beta and PD-L1 in Pancreatic Cancer
by Ingrid Garajová, Andrea Cavazzoni, Michela Verze, Roberta Minari, Giuseppe Pedrazzi, Rita Balsano, Fabio Gelsomino, Raffaele Dalla Valle, Graziana Digiacomo, Elisa Giovannetti and Francesco Leonardi
Life 2022, 12(7), 960; https://0-doi-org.brum.beds.ac.uk/10.3390/life12070960 - 26 Jun 2022
Cited by 1 | Viewed by 1492
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechanisms underlying PDAC aggressiveness and immune evasion, soluble TGF-beta (sTGF-beta) and sPD-L1, in both metastatic and radically-resected PDAC. To this aim we prospectively enrolled 38 PDAC patients and performed appropriate statistical analyses in order to evaluate their correlation, and role in the prediction of disease relapse/progression, and patients’ outcome. Results: Metastatic patients showed lower levels of circulating sTGF-beta and higher levels of sPD-L1 compared to radically-resected patients. Moreover, a decrease in sTGF-beta levels (but not sPD-L1) was significantly associated with disease relapse in radically-resected patients. We also observed lower sTGF-beta at disease progression after first-line chemotherapy in metastatic patients, though this change was not statistically significant. We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. Conclusions: These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers. Full article
(This article belongs to the Special Issue New Therapeutic Strategies in Pancreatic Cancer)
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10 pages, 1849 KiB  
Article
Protective or Risk Factors for Postoperative Pancreatic Fistulas in Malignant Pathology
by Alin Mihai Vasilescu, Delia Florina Andriesi Rusu, Costel Bradea, Nutu Vlad, Corina Lupascu-Ursulescu, Irene Alexandra Spiridon, Ana Maria Trofin, Eugen Tarcoveanu and Cristian Dumitru Lupascu
Life 2021, 11(11), 1216; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111216 - 10 Nov 2021
Cited by 2 | Viewed by 1599
Abstract
Introduction: Malignant tumors are associated with a low incidence of postoperative pancreatic fistulas. The presence of peritumoral fibrosis is considered the protective factor for the development of postoperative pancreatic fistulas after pancreatic resections for pancreatic ductal adenocarcinomas. Methods: We analyzed a series of [...] Read more.
Introduction: Malignant tumors are associated with a low incidence of postoperative pancreatic fistulas. The presence of peritumoral fibrosis is considered the protective factor for the development of postoperative pancreatic fistulas after pancreatic resections for pancreatic ductal adenocarcinomas. Methods: We analyzed a series of 109 consecutive patients with pancreatic resections for malignant pathology: pancreatic ductal adenocarcinomas and periampullary adenocarcinomas. The incidence of postoperative pancreatic fistulas has been reported in tumor histological type, in the presence of peritumoral fibrosis, and in the association between adenocarcinomas and areas of acute pancreatitis. The data obtained were processed with the statistical analysis program SPSS, and statistically significant p were considered at a value <0.05. Results: For the entire study group, the incidence of postoperative pancreatic fistulas was 11.01%. The lowest incidence was observed in the group of patients with pancreatic ductal adenocarcinomas (4.06% vs. 25.72% in the group with periampullary adenocarcinoma), with a p = 0.002. The presence of peritumoral fibrous tissue was observed in 49.31% of cases without pancreatic fistulas, and in 54.54% of cases that developed this postoperative complication (p = 0.5). Also, the peritumoral fibrous tissue had a uniform distribution depending on the main diagnosis (56.14% in pancreatic ductal adenocarcinoma group vs. 37.04% in periampullary adenocarcinoma group, with a p = 0.08). In the group of patients who associated areas of acute pancreatitis on the resections, the incidence of postoperative pancreatic fistulas was 7.8 times higher (30% vs. 3.8%, p = 0.026). Conclusions: Peritumoral fibrous tissue was not a factor involved in the developing of postoperative pancreatic fistulas. The association of adenocarciomas with areas of acute pancreatitis has led to a significant increase in postoperative pancreatic fistulas, which is a significant and independent risk factor. Full article
(This article belongs to the Special Issue New Therapeutic Strategies in Pancreatic Cancer)
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Review

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22 pages, 1999 KiB  
Review
Ablative Radiotherapy (ART) for Locally Advanced Pancreatic Cancer (LAPC): Toward a New Paradigm?
by Nicola Simoni, Gabriella Rossi, Francesco Cellini, Viviana Vitolo, Ester Orlandi, Vincenzo Valentini, Renzo Mazzarotto, Nicola Sverzellati and Nunziata D’Abbiero
Life 2022, 12(4), 465; https://0-doi-org.brum.beds.ac.uk/10.3390/life12040465 - 22 Mar 2022
Cited by 2 | Viewed by 2856
Abstract
Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of [...] Read more.
Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed. Full article
(This article belongs to the Special Issue New Therapeutic Strategies in Pancreatic Cancer)
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17 pages, 3146 KiB  
Review
Target Nanoparticles against Pancreatic Cancer: Fewer Side Effects in Therapy
by Jorge A. Roacho-Pérez, Elsa N. Garza-Treviño, Paulina Delgado-Gonzalez, Zuca G-Buentello, Juan Luis Delgado-Gallegos, Christian Chapa-Gonzalez, Margarita Sánchez-Domínguez, Celia N. Sánchez-Domínguez and Jose Francisco Islas
Life 2021, 11(11), 1187; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111187 - 5 Nov 2021
Cited by 12 | Viewed by 3554
Abstract
Pancreatic cancer is the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve the non-specific use of chemotherapeutical agents such as 5-FU, capecitabine, gemcitabine, paclitaxel, cisplatin, oxaliplatin, or irinotecan, which produce several side effects. This [...] Read more.
Pancreatic cancer is the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve the non-specific use of chemotherapeutical agents such as 5-FU, capecitabine, gemcitabine, paclitaxel, cisplatin, oxaliplatin, or irinotecan, which produce several side effects. This review focuses on the use of targeted nanoparticles, such as metallic nanoparticles, polymeric nanoparticles, liposomes, micelles, and carbon nanotubes as an alternative to standard treatment for pancreatic cancer. The principal objective of nanoparticles is reduction of the side effects that conventional treatments produce, mostly because of their non-specificity. Several molecular markers of pancreatic cancer cells have been studied to target nanoparticles and improve current treatment. Therefore, properly functionalized nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells. Once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, gene therapy, or hyperthermia. Full article
(This article belongs to the Special Issue New Therapeutic Strategies in Pancreatic Cancer)
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Other

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16 pages, 2131 KiB  
Systematic Review
A Review on the Efficacy and Safety of Nab-Paclitaxel with Gemcitabine in Combination with Other Therapeutic Agents as New Treatment Strategies in Pancreatic Cancer
by Christian Chapa-González, Karina López, Kimberly Michelle Lomelí, Jorge Alberto Roacho-Pérez and Jazmín Cristina Stevens
Life 2022, 12(3), 327; https://0-doi-org.brum.beds.ac.uk/10.3390/life12030327 - 22 Feb 2022
Cited by 6 | Viewed by 3667
Abstract
Pancreatic cancer has one of the highest mortality rates among cancers, and a combination of nab-paclitaxel with gemcitabine remains the cornerstone of first-line therapy. However, major advances are required to achieve improvements in patient outcomes. For this reason, several research groups have proposed [...] Read more.
Pancreatic cancer has one of the highest mortality rates among cancers, and a combination of nab-paclitaxel with gemcitabine remains the cornerstone of first-line therapy. However, major advances are required to achieve improvements in patient outcomes. For this reason, several research groups have proposed supplementing treatment with other therapeutic agents. Ongoing studies are being conducted to find the optimal treatment in a first-line setting. In this work, we used a search strategy to compare studies on the efficacy and safety of nab-paclitaxel with gemcitabine in combination with other therapeutic agents based on the criteria of the Preferred Reporting Items for Systematic Reviews. We found seven studies in different clinical phases that met the inclusion criteria. The seven therapeutic agents were ibrutinib, necuparanib, tarextumab, apatorsen, cisplatin, enzalutamide, and momelotinib. Although these therapeutic agents have different mechanisms of action, and molecular biology studies are still needed, the present review was aimed to answer the following question: which formulations of the nab-paclitaxel/gemcitabine regimen in combination with other therapeutic agents are safest for patients with previously untreated metastatic pancreas ductal adenocarcinoma? The triple regimen is emerging as the first-line option for patients with pancreatic cancer, albeit with some limitations. Thus, further studies of this regimen are recommended. Full article
(This article belongs to the Special Issue New Therapeutic Strategies in Pancreatic Cancer)
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