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16 pages, 2591 KiB

Open AccessArticle

Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer

by Erica Yada, Rika Kasajima, Atsushi Niida, Seiya Imoto, Satoru Miyano, Yohei Miyagi, Tetsuro Sasada and Satoshi Wada

Biomedicines 2021, 9(10), 1396; https://doi.org/10.3390/biomedicines9101396 - 05 Oct 2021

Cited by 9 | Viewed by 1915

Abstract

Patient-derived xenograft models reportedly represent original tumor morphology and gene mutation profiles. In addition, patient-derived xenografts are expected to recapitulate the parental tumor drug responses. In this study, we analyzed the pathways involved in gemcitabine resistance using patient-derived xenograft models of pancreatic cancer. [...] Read more.

Patient-derived xenograft models reportedly represent original tumor morphology and gene mutation profiles. In addition, patient-derived xenografts are expected to recapitulate the parental tumor drug responses. In this study, we analyzed the pathways involved in gemcitabine resistance using patient-derived xenograft models of pancreatic cancer. The patient-derived xenograft models were established using samples from patients with pancreatic cancer. The models were treated with gemcitabine to better understand the mechanism of resistance to this anti-cancer drug. We performed comparative gene analysis through the next-generation sequencing of tumor tissues from gemcitabine-treated or non-treated patient-derived xenograft mice and gene set enrichment analysis to analyze mRNA profiling data. Pathway analysis of gemcitabine-treated patient-derived xenografts disclosed the upregulation of multiple gene sets and identified several specific gene pathways that could potentially be related to gemcitabine resistance in pancreatic cancer. Further, we conducted an in vitro analysis to validate these results. The mRNA expression of cytochrome P450 1B1 and cytochrome P450 2A6 was upregulated in a concentration-dependent manner following gemcitabine treatment. Moreover, the sensitivity to gemcitabine increased, and viable cells were decreased by the cytochrome P450 1B1 inhibitor, indicating that the cytochrome P450 1B1 pathway may be related to gemcitabine resistance in pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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23 pages, 8140 KiB

Open AccessArticle

Soluble Compounds Released by Hypoxic Stroma Confer Invasive Properties to Pancreatic Ductal Adenocarcinoma

by Dajia Liu, Anne Steins, Remy Klaassen, Amber P. van der Zalm, Roel J. Bennink, Geertjan van Tienhoven, Marc G. Besselink, Maarten F. Bijlsma and Hanneke W. M. van Laarhoven

Biomedicines 2020, 8(11), 444; https://doi.org/10.3390/biomedicines8110444 - 22 Oct 2020

Cited by 6 | Viewed by 2524

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and a hypoxic microenvironment. Pancreatic stellate cells (PSC) are activated by hypoxia and promote excessive desmoplasia, further contributing to the development of hypoxia. We aimed to explore how hypoxia and stroma interact to contribute [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and a hypoxic microenvironment. Pancreatic stellate cells (PSC) are activated by hypoxia and promote excessive desmoplasia, further contributing to the development of hypoxia. We aimed to explore how hypoxia and stroma interact to contribute to invasive growth in PDAC. [¹⁸F]HX4 PET/CT was found to be a feasible non-invasive method to assess tumor hypoxia in 42 patients and correlated with HIF1α immunohistochemistry in matched surgical specimens. [¹⁸F]HX4 uptake and HIF1α were strong prognostic markers for overall survival. Co-culture and medium transfer experiments demonstrated that hypoxic PSCs and their supernatant induce upregulation of mesenchymal markers in tumor cells, and that hypoxia-induced stromal factors drive invasive growth in hypoxic PDACs. Through stepwise selection, stromal MMP10 was identified as the most likely candidate responsible for this. In conclusion, hypoxia-activated PSCs promote the invasiveness of PDAC through paracrine signaling. The identification of PSC-derived MMP10 may provide a lead to develop novel stroma-targeting therapies. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 2208 KiB

Open AccessArticle

Vav1 Down-Modulates Akt2 Expression in Cells from Pancreatic Ductal Adenocarcinoma: Nuclear Vav1 as a Potential Regulator of Akt Related Malignancy in Pancreatic Cancer

by Silvia Grassilli, Federica Brugnoli, Rossano Lattanzio, Simonetta Buglioni and Valeria Bertagnolo

Biomedicines 2020, 8(10), 379; https://doi.org/10.3390/biomedicines8100379 - 26 Sep 2020

Cited by 6 | Viewed by 2097

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive tumor malignancy worldwide, mainly due to uncontrolled metastasis. Among the numerous molecules deregulated in PDAC, different members of the Akt pathways are of great importance because they are involved in tumor cell proliferation, migration, and [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive tumor malignancy worldwide, mainly due to uncontrolled metastasis. Among the numerous molecules deregulated in PDAC, different members of the Akt pathways are of great importance because they are involved in tumor cell proliferation, migration, and invasion. We have recently demonstrated that Vav1, ectopically expressed in solid tumors, is capable of down-modulating expression and/or activation of specific Akt isoforms in breast cancer cells. By using pancreatic cell lines expressing different basal levels of Vav1, we demonstrated here that Vav1 down-regulates the expression of Akt2, known to correlate with tumor metastases and resistance to therapy. In particular, while the silencing of Vav1 is sufficient to induce Akt2, its up-modulation reduces Akt2 levels only when Vav1 accumulates inside the nucleus of PDAC cells. Moreover, in PDAC tissues, we revealed that high nuclear levels of Vav1 correlate with low Akt2 expression. Although we cannot demonstrate the mechanisms involved, our results provide new insights into the role of Vav1 in PDAC and, as targeting specific members of the Akt family is a promising therapeutic chance in solid tumors, they suggest that Vav1, by down-modulating Akt2, has potential as a molecular target in PDAC. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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Review

Jump to: Research

21 pages, 660 KiB

Open AccessReview

The Latest Advancement in Pancreatic Ductal Adenocarcinoma Therapy: A Review Article for the Latest Guidelines and Novel Therapies

by Marwa Elsayed and Maen Abdelrahim

Biomedicines 2021, 9(4), 389; https://doi.org/10.3390/biomedicines9040389 - 06 Apr 2021

Cited by 22 | Viewed by 3880

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable micro-metastasis at the time of presentation play a vital role in the high death rate from pancreatic cancer. In addition to this, the low mutation burden in pancreatic cancer, low immunological profile, dense tumorigenesis stroma, and decreased tumor sensitivity to cytotoxic drugs contribute to the low survival rates in PDAC patients. Despite breakthroughs in chemotherapeutic and immunotherapeutic drugs, pancreatic cancer remains one of the solid tumors that exhibit meager curative rates. Therefore, researchers must dedicate more effort to understanding the pathology and immunological behavior of PDAC, in addition to properly utilizing more advanced screening modalities and new therapeutic agents. In our review, we focus mainly on the latest updates from clinical guidelines and novel therapies that have been recently investigated or are under investigation for PDAC. We used PubMed as a search tool for finding original research articles addressing the latest developments in diagnosing and treating PDAC. Additionally, we also used the clinical trials published on clinicaltrialsgov as sources for our data. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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23 pages, 1276 KiB

Open AccessReview

Pancreatic Cancer Signaling Pathways, Genetic Alterations, and Tumor Microenvironment: The Barriers Affecting the Method of Treatment

by Darya Javadrashid, Amir Baghbanzadeh, Afshin Derakhshani, Patrizia Leone, Nicola Silvestris, Vito Racanelli, Antonio Giovanni Solimando and Behzad Baradaran

Biomedicines 2021, 9(4), 373; https://doi.org/10.3390/biomedicines9040373 - 02 Apr 2021

Cited by 50 | Viewed by 6426

Abstract

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune [...] Read more.

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune evasion of pancreatic malignant cells. Mastering the mechanisms of these two hallmarks of PDAC can help us in dealing with the obstacles in the way of treatment. In this review, we have analyzed the signaling pathways involved in PDAC development and the immune system’s role in pancreatic cancer and immune checkpoint inhibition as next-generation therapeutic strategy. The direct targeting of the involved signaling molecules and the immune checkpoint molecules, along with a combination with conventional therapies, have reached the most promising results in pancreatic cancer treatment. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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25 pages, 5330 KiB

Open AccessReview

Exosomes as Pleiotropic Players in Pancreatic Cancer

by Laura De Lellis, Rosalba Florio, Maria Cristina Di Bella, Davide Brocco, Francesca Guidotti, Nicola Tinari, Antonino Grassadonia, Rossano Lattanzio, Alessandro Cama and Serena Veschi

Biomedicines 2021, 9(3), 275; https://doi.org/10.3390/biomedicines9030275 - 09 Mar 2021

Cited by 14 | Viewed by 3178

Abstract

Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response to current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis is of paramount importance for rational diagnostic [...] Read more.

Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response to current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis is of paramount importance for rational diagnostic and therapeutic approaches. Multiple lines of evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos of bioactive molecules to recipient cells within the tumor microenvironment and systemically. Intriguingly, exosomes may exert both protumor and antitumor effects, supporting or hampering processes that play a role in the pathogenesis and progression of PC, including shifts in tumor metabolism, proliferation, invasion, metastasis, and chemoresistance. They also have a dual role in PC immunomodulation, exerting immunosuppressive or immune enhancement effects through several mechanisms. PC-derived exosomes also induce systemic metabolic alterations, leading to the onset of diabetes and weight loss. Moreover, exosomes have been described as promising diagnostic and prognostic biomarkers for PC. Their potential application in PC therapy as drug carriers and therapeutic targets is under investigation. In this review, we provide an overview of the multiple roles played by exosomes in PC biology through their specific cargo biomolecules and of their potential exploitation in early diagnosis and treatment of PC. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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29 pages, 1726 KiB

Open AccessReview

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

by Seung Wan Son, Mun Gyu Song, Ba Da Yun and Jong Kook Park

Biomedicines 2021, 9(3), 263; https://doi.org/10.3390/biomedicines9030263 - 07 Mar 2021

Cited by 7 | Viewed by 2650

Abstract

Therapeutic resistance is an inevitable impediment towards effective cancer therapies. Evidence accumulated has shown that the signaling pathways and related factors are fundamentally responsible for therapeutic resistance via regulating diverse cellular events, such as epithelial-to-mesenchymal transition (EMT), stemness, cell survival/apoptosis, autophagy, etcetera. Noncoding [...] Read more.

Therapeutic resistance is an inevitable impediment towards effective cancer therapies. Evidence accumulated has shown that the signaling pathways and related factors are fundamentally responsible for therapeutic resistance via regulating diverse cellular events, such as epithelial-to-mesenchymal transition (EMT), stemness, cell survival/apoptosis, autophagy, etcetera. Noncoding RNAs (ncRNAs) have been identified as essential cellular components in gene regulation. The expression of ncRNAs is altered in cancer, and dysregulated ncRNAs participate in gene regulatory networks in pathological contexts. An in-depth understanding of molecular mechanisms underlying the modulation of therapeutic resistance is required to refine therapeutic benefits. This review presents an overview of the recent evidence concerning the role of human ncRNAs in therapeutic resistance, together with the feasibility of ncRNAs as therapeutic targets in pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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33 pages, 10173 KiB

Open AccessReview

Therapeutic Status and Available Strategies in Pancreatic Ductal Adenocarcinoma

by Gitika Thakur, Raj Kumar, Saet-Byul Kim, Sang-Yeob Lee, Sung-Lim Lee and Gyu-Jin Rho

Biomedicines 2021, 9(2), 178; https://doi.org/10.3390/biomedicines9020178 - 11 Feb 2021

Cited by 9 | Viewed by 4201

Abstract

One of the most severe and devastating cancer is pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the major pancreatic exocrine cancer with a poor prognosis and growing prevalence. It is the most deadly disease, with an overall five-year survival rate of [...] Read more.

One of the most severe and devastating cancer is pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the major pancreatic exocrine cancer with a poor prognosis and growing prevalence. It is the most deadly disease, with an overall five-year survival rate of 6% to 10%. According to various reports, it has been demonstrated that pancreatic cancer stem cells (PCSCs) are the main factor responsible for the tumor development, proliferation, resistance to anti-cancer drugs, and recurrence of tumors after surgery. PCSCs have encouraged new therapeutic methods to be explored that can specifically target cancer cells. Furthermore, stem cells, especially mesenchymal stem cells (MSCs), are known as influential anti-cancer agents as they function through anti-inflammatory, paracrine, cytokines, and chemokine′s action. The properties of MSCs, such as migration to the site of infection and host immune cell activation by its secretome, seem to control the microenvironment of the pancreatic tumor. MSCs secretome exhibits similar therapeutic advantages as a conventional cell-based therapy. Moreover, the potential for drug delivery could be enhanced by engineered MSCs to increase drug bioactivity and absorption at the tumor site. In this review, we have discussed available therapeutic strategies, treatment hurdles, and the role of different factors such as PCSCs, cysteine, GPCR, PKM2, signaling pathways, immunotherapy, and NK-based therapy in pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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21 pages, 993 KiB

Open AccessReview

The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

by Sona Ciernikova, Maria Novisedlakova, Danka Cholujova, Viola Stevurkova and Michal Mego

Biomedicines 2020, 8(12), 565; https://doi.org/10.3390/biomedicines8120565 - 03 Dec 2020

Cited by 15 | Viewed by 3493

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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32 pages, 2988 KiB

Open AccessReview

Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials

by Isabel Mejia, Sandhya Bodapati, Kathryn T. Chen and Begoña Díaz

Biomedicines 2020, 8(10), 401; https://doi.org/10.3390/biomedicines8100401 - 09 Oct 2020

Cited by 5 | Viewed by 3514

Abstract

Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of [...] Read more.

Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of PDAC and modulate the reciprocal interactions between cancer and stromal cells in ways that have profound effects in the pathophysiology and treatment of this disease. Here, we review some of the most recent findings regarding the regulation of PDAC cell invasion by the unique microenvironment of this tumor, and how new knowledge is being translated into novel therapeutic approaches. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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15 pages, 770 KiB

Open AccessReview

Targeting Mutant KRAS in Pancreatic Cancer: Futile or Promising?

by Friederike Inga Nollmann and Dietrich Alexander Ruess

Biomedicines 2020, 8(8), 281; https://doi.org/10.3390/biomedicines8080281 - 11 Aug 2020

Cited by 25 | Viewed by 4598

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers with a dismal prognosis for the patient. This is due to limited diagnostic options for the early detection of the disease as well as its rather aggressive nature. Despite major advances in [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers with a dismal prognosis for the patient. This is due to limited diagnostic options for the early detection of the disease as well as its rather aggressive nature. Despite major advances in oncologic research in general, the treatment options in the clinic for PDAC have only undergone minor changes in the last decades. One major treatment advance would be the successful targeting of the oncogenic driver KRAS^mut. In the past, the indirect targeting of KRAS has been exploited, e. g., via upstream inhibition of receptor tyrosine kinases or via downstream MEK or PI3K inhibition. However, the experience gained from clinical trials and from the clinic itself in the treatment of KRAS^mut cancer entities has dampened the initial euphoria. Lately, with the development of KRAS^G12C-specific inhibitors, not only the direct but also the indirect targeting of KRAS^mut has gained momentum again. Though preclinical studies and preliminary early clinical studies of monotherapies have shown promising results, they have been overshadowed by the swift development of resistances resulting in inconsistent responses in patient cohorts. Currently, several different combination therapies for KRAS^mut cancer are being explored. If they hold the promise they have made in preclinical studies, they might also be suitable treatment options for patients suffering from PDAC. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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23 pages, 1777 KiB

Open AccessEditor’s ChoiceReview

Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies

by Gabriela Reyes-Castellanos, Rawand Masoud and Alice Carrier

Biomedicines 2020, 8(8), 270; https://doi.org/10.3390/biomedicines8080270 - 03 Aug 2020

Cited by 39 | Viewed by 5787

Abstract

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. [...] Read more.

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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28 pages, 1241 KiB

Open AccessReview

Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

by Sokviseth Moeng, Seung Wan Son, Jong Sun Lee, Han Yeoung Lee, Tae Hee Kim, Soo Young Choi, Hyo Jeong Kuh and Jong Kook Park

Biomedicines 2020, 8(8), 267; https://doi.org/10.3390/biomedicines8080267 - 03 Aug 2020

Cited by 23 | Viewed by 4943

Abstract

Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of [...] Read more.

Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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14 pages, 1079 KiB

Open AccessReview

Defining Parallels between the Salivary Glands and Pancreas to Better Understand Pancreatic Carcinogenesis

by Céline Tiffon

Biomedicines 2020, 8(6), 178; https://doi.org/10.3390/biomedicines8060178 - 26 Jun 2020

Cited by 9 | Viewed by 6623

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis, largely due to its late presentation. Methods for early detection, the development of reliable screening tools, and the identification of sensitive and specific biomarkers have remained essential research priorities to [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis, largely due to its late presentation. Methods for early detection, the development of reliable screening tools, and the identification of sensitive and specific biomarkers have remained essential research priorities to improve early patient management and outcomes. The pancreas and salivary glands share histological and functional similarities, and the salivary glands have demonstrated a role in oral and systemic health. This review focuses on the similarities and differences between the pancreas and salivary glands and how these can inform our understanding of PDAC genesis and early diagnosis. In particular, chemical exposure, which alters salivary gland gene transcription and morphogenesis, may not only directly impact salivary gland regulation but alter pancreatic function via the systemic secretion of growth hormones. Diabetes and obesity are associated with an increased risk of pancreatic cancer, and a link between chemical exposure and the development of diabetes, obesity, and consequently PDAC genesis is proposed. Possible mechanisms include altering salivary or pancreatic morphology and organ function, disrupting endocrine signaling, or altering pro-inflammatory homeostasis. Finally, saliva contains putative specific biomarkers that show promise as non-invasive diagnostic tools for PDAC. Full article

(This article belongs to the Special Issue Pancreatic Ductal Adenocarcinoma: From Pathophysiology to Novel Therapeutic Approaches)

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