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Cancers
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Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?
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Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 12189

Special Issue Editor

Prof. Dr. Jean Luc B. van Laethem

E-Mail Website
Guest Editor
Department of Digestive Oncology, Erasme Hospital and Bordet Institute, Université Libre de Bruxelles, 1070 Brussels, Belgium
Interests: gastrointestinal oncology; pancreatic cancer research; new drugs

Special Issue Information

Dear Colleagues,

We would like to invite you to submit either original research or review articles for this Special Issue on “Combination Therapies for Pancreatic Cancer: How to Make Progress?”  The journal has an impact factor of 6.639, and you are receiving this letter as a personal invitation on behalf of one of the Editors.

This Special Issue will focus on the recent advances in the field of PDAC treatment, focusing on new combinations in systemic therapies in metastatic settings but also on combining loco-regional approaches. The topics will include, but are not limited to, advances in: (1) chemotherapy as a backbone for new combinations with anti-metabolic drugs; (2) the emergence of targeting BRCAness; (3) new immuno(chemo)therapeutic combinations for PDAC subtypes; (4) targeting the pancreatic tumor microenvironment; (5) the potential role of CDK 4/6; (6) potential partners for radiation therapy; (7) new combinational approaches in locally advanced tumors; and (8) precision medicine in PDAC: practical approaches.

Thank you for your consideration.

Kind regards,
Prof. Dr. Jean Luc B. van Laethem
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

  • pancreatic cancer
  • systemic therapy
  • molecular-driven therapy
  • immunotherapy
  • new translational combinations

Published Papers (6 papers)

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Research

Jump to: Review, Other

20 pages, 2621 KiB  
Article
Immunomodulatory Effects of Endoscopic Ultrasound-Guided Thermal Ablation in Patients with Pancreatic Ductal Adenocarcinoma
by Sabrina Gloria Giulia Testoni, Claudia Minici, Elisa Benetti, Francesca Clemente, Daniela Boselli, Clara Sciorati, Lucia De Monte, Maria Chiara Petrone, Markus Enderle, Walter Linzenbold, Maria Pia Protti, Angelo Manfredi, Francesco De Cobelli, Michele Reni, Massimo Falconi, Gabriele Capurso, Paolo Giorgio Arcidiacono and Emanuel Della-Torre
Cancers 2023, 15(14), 3704; https://doi.org/10.3390/cancers15143704 - 21 Jul 2023
Viewed by 1108
Abstract
Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable [...] Read more.
Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable and locally advanced PDAC, randomly allocated to Nab-paclitaxel plus Gemcitabine chemotherapy (CT-arm, n = 5) or EUS-LTA with HybridTherm Probe plus CT (HTP + CT-arm, n = 5). Twenty healthy donors were included as controls. Flow-cytometry and multiplex assays were used to profile immune cell subsets and measure serum cytokines/chemokines, respectively. At baseline, PDAC patients showed increased circulating monocytes and lower circulating lymphocytes and CD19+ B cells counts compared to healthy controls. After 4 months, CT induced decrease of B regulatory cells, CD4+ cytotoxic T cells and IL-1β. The addition of EUS-HTP to CT selectively decreased the serum levels of APRIL/TNFSF13 as well as T regulatory cells, total, classic and inflammatory monocytes. Serum levels of APRIL/TNFSF13 and total, classic and inflammatory monocytes counts at baseline were associated with worse overall survival. EUS-HTP has the potential to selectively impact on immune cells and cytokines associated with poor outcomes in PDAC. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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Review

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18 pages, 841 KiB  
Review
Pancreatic Cancer: BRCA Targeted Therapy and Beyond
by Fergus Keane, Catherine A. O’Connor, Wungki Park, Thomas Seufferlein and Eileen M. O’Reilly
Cancers 2023, 15(11), 2955; https://doi.org/10.3390/cancers15112955 - 28 May 2023
Cited by 2 | Viewed by 2800
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death in the US by 2030, despite accounting for only 5% of all cancer diagnoses. Germline gBRCA1/2-mutated PDAC represents a key subgroup with a favorable prognosis, due [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death in the US by 2030, despite accounting for only 5% of all cancer diagnoses. Germline gBRCA1/2-mutated PDAC represents a key subgroup with a favorable prognosis, due at least in part to additional approved and guideline-endorsed therapeutic options compared with an unselected PDAC cohort. The relatively recent incorporation of PARP inhibition into the treatment paradigm for such patients has resulted in renewed optimism for a biomarker-based approach to the management of this disease. However, gBRCA1/2 represents a small subgroup of patients with PDAC, and efforts to extend the indication for PARPi beyond BRCA1/2 mutations to patients with PDAC and other genomic alterations associated with deficient DNA damage repair (DDR) are ongoing, with several clinical trials underway. In addition, despite an array of approved therapeutic options for patients with BRCA1/2-associated PDAC, both primary and acquired resistance to platinum-based chemotherapies and PARPi presents a significant challenge in improving long-term outcomes. Herein, we review the current treatment landscape of PDAC for patients with BRCA1/2 and other DDR gene mutations, experimental approaches under investigation or in development, and future directions. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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21 pages, 1829 KiB  
Review
CDK4/6 Inhibitors in Pancreatobiliary Cancers: Opportunities and Challenges
by Tatjana Arsenijevic, Katia Coulonval, Eric Raspé, Anne Demols, Pierre P. Roger and Jean-Luc Van Laethem
Cancers 2023, 15(3), 968; https://doi.org/10.3390/cancers15030968 - 03 Feb 2023
Cited by 3 | Viewed by 2636
Abstract
Existing treatment strategies for pancreatobiliary malignancies are limited. Nowadays, surgery is the only path to cure these types of cancer, but only a small number of patients present with resectable tumors at the time of diagnosis. The notoriously poor prognosis, lack of diverse [...] Read more.
Existing treatment strategies for pancreatobiliary malignancies are limited. Nowadays, surgery is the only path to cure these types of cancer, but only a small number of patients present with resectable tumors at the time of diagnosis. The notoriously poor prognosis, lack of diverse treatment options associated with pancreaticobiliary cancers, and their resistance to current therapies reflect the urge for the development of novel therapeutic targets. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as an attractive therapeutic strategy in a number of cancers since their approval for treatment in patients with ER+/HER- breast cancer in combination with antiestrogens. In this article, we discuss the therapeutic potential of CDK4/6 inhibitors in pancreatobiliary cancers, notably cholangiocarcinoma and pancreatic ductal adenocarcinoma. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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26 pages, 1610 KiB  
Review
Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?
by Sofian Benkhaled, Cedric Peters, Nicolas Jullian, Tatjana Arsenijevic, Julie Navez, Dirk Van Gestel, Luigi Moretti, Jean-Luc Van Laethem and Christelle Bouchart
Cancers 2023, 15(3), 768; https://doi.org/10.3390/cancers15030768 - 26 Jan 2023
Cited by 2 | Viewed by 2255
Abstract
Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop [...] Read more.
Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC’s tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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27 pages, 1236 KiB  
Review
The Microbiome in PDAC—Vantage Point for Future Therapies?
by Nina Pfisterer, Catharina Lingens, Cathleen Heuer, Linh Dang, Albrecht Neesse and Christoph Ammer-Herrmenau
Cancers 2022, 14(23), 5974; https://doi.org/10.3390/cancers14235974 - 02 Dec 2022
Cited by 5 | Viewed by 1845
Abstract
Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to [...] Read more.
Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to understand and exploit this knowledge for the treatment of human malignancies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor with limited therapeutic options and a poor long-term survival. Recent data have revealed fascinating insights into the role of the tumoral microbiome in PDAC, with profound implications for survival and potentially therapeutic outcomes. In this review, we outline the current scientific knowledge about the clinical and translational role of the microbiome in PDAC. We describe the microbial compositions in healthy and tumoral pancreatic tissue and point out four major aspects of the microbiome in PDAC: pathogenesis, diagnosis, treatment, and prognosis. However, caution must be drawn to inherent pitfalls in analyzing the intratumoral microbiome. Among others, contamination with environmental microbes is one of the major challenges. To this end, we discuss different decontamination approaches that are crucial for clinicians and scientists alike to foster applicability and physiological relevance in this translational field. Without a definition of an exact and reproducible intratumoral microbial composition, the exploitation of the microbiome as a diagnostic or therapeutic tool remains theoretical. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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Other

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19 pages, 1901 KiB  
Systematic Review
Normo- or Hypo-Fractionated Photon or Proton Radiotherapy in the Management of Locally Advanced Unresectable Pancreatic Cancer: A Systematic Review
by Sally A. Elkhamisy, Chiara Valentini, Annika Lattermann, Ganesh Radhakrishna, Luise A. Künzel, Steffen Löck and Esther G. C. Troost
Cancers 2023, 15(15), 3771; https://doi.org/10.3390/cancers15153771 - 25 Jul 2023
Viewed by 974
Abstract
LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, [...] Read more.
LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, in treatment outcomes and their respective toxicity profiles. Methods: Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed. Results: A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3–22.9 months and 8.5–20 months, respectively. For the PBT group, the range of median OS was 18.4–22.3 months. Conclusion: CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety. Full article
(This article belongs to the Special Issue Combination Therapies for Pancreatic Cancer: How to Make Comprehensive Progress?)
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