Special Issue "Pancreatic Cancer: Challenges and Breakthroughs"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 15 May 2021.

Special Issue Editor

Dr. Maria Del Pilar Acedo Nunez
E-Mail Website
Guest Editor
Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital Campus, University College London, London, UK
Interests: pancreatic cancer; cholangiocarcinoma; early diagnosis; photodynamic therapy; nanomedicine; organoids

Special Issue Information

Dear Colleagues,

Pancreatic cancer is an extremely lethal disease. It is difficult to detect early due to patients presenting vague symptoms, and thus is difficult to treat effectively leading to high rates of recurrence. Although advances in imaging techniques have been made, current imaging methods and biomarker panels to detect the disease in patients at high-risk of developing cancer, lack the necessary sensitivity and specificity for routine use in early detection screenings. Over the last years, many preclinical studies and clinical trials have been conducted trying to improve patient outcomes. Altogether, those studies led to deepening our understanding of disease development and progression, and to deciphering molecular pathways and mechanisms of resistance to therapy. Nonetheless, some key challenges remain to be addressed. Because of those, current efforts seek to advance research progress toward: a) improving treatment options and establishing new therapeutic strategies to overcome drug resistance; b) discovering new drug targets; c) performing molecular profiling; and d) advancing early detection.

The present Special Issue aims to address “Pancreatic Cancer: Challenges and Breakthroughs” by assembling significant contributions in the following categories:

  1. Present challenges: future directions for improving outcomes
  2. Novel therapeutic strategies, such as but not limited to: personalized medicine, combination and targeted therapy, immunotherapy, new therapeutic targets, tumor metabolism
  3. Insights into early detection: biomarkers, new imaging techniques, AI
  4. Tumor microenvironment: tumor microbiome, disease modeling, tumor-stroma interactions, inflammation
  5. Drug resistance and disease recurrence: prognostic markers, cancer stem cells, circulating tumor cells, tumor heterogeneity

I hope this scope will encourage the participation of researchers and clinicians, who would like to address future directions to improve the outcome of pancreatic cancer patients. Contributions can be made in the format of research articles, reviews, communications, perspectives, opinions, concept papers, and case studies.

Dr. Maria Del Pilar Acedo Nunez
Guest Editor

Manuscript Submission Information

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Keywords

  • Novel therapeutics
  • Early detection
  • Tumor microenvironment
  • Disease recurrence
  • Resistance

Published Papers (13 papers)

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Research

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Open AccessArticle
Clinical Phase I/II Study: Local Disease Control and Survival in Locally Advanced Pancreatic Cancer Treated with Electrochemotherapy
J. Clin. Med. 2021, 10(6), 1305; https://doi.org/10.3390/jcm10061305 - 22 Mar 2021
Viewed by 434
Abstract
Objective. To assess local disease control rates (LDCR) and overall survival (OS) in locally advanced pancreatic cancer (LAPC) treated with electrochemotherapy (ECT). Methods. Electrochemotherapy with bleomycin was performed in 25 LAPC patients who underwent baseline Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) [...] Read more.
Objective. To assess local disease control rates (LDCR) and overall survival (OS) in locally advanced pancreatic cancer (LAPC) treated with electrochemotherapy (ECT). Methods. Electrochemotherapy with bleomycin was performed in 25 LAPC patients who underwent baseline Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and Position Emission Tomography (PET) scans before ECT and 1 and 6 months post ECT. LDCR were assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Choi criteria. Needle electrodes with fixed linear (N-30-4B) or fixed hexagonal configurations (N-30-HG or I-40-HG or H-30-ST) or variable geometry (VGD1230 or VGD1240) (IGEA S.p.A., Carpi, Italy) were used to apply electric pulses. Pain evaluation was performed pre-ECT, after 1 month and after 6 months with ECT. Overall survival estimates were calculated by means of a Kaplan-Meier analysis. Results. At 1 month after ECT, 76% of patients were in partial response (PR) and 20% in stable disease (SD). Six months after ECT, 44.0% patients were still in PR and 12.0% in SD. A LDCR of 56.0% was reached six months after ECT: 13 patients treated with fixed geometry had a LDCR of 46.1%, while for the 12 patients treated with variable geometry, the LDCR was 66.7%. The overall survival median value was 11.5 months: for patients treated with fixed geometry the OS was 6 months, while for patients treated with variable geometry it was 12 months. Electrochemotherapy was well-tolerated and abdominal pain was rapidly resolved. Conclusions. Electrochemotherapy obtained good results in terms of LDCR and OS in LAPC. Multiple needle insertion in a variable geometry configuration optimized by pre-treatment planning determined an increase in LDCR and OS compared to a fixed geometry configuration. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessArticle
Is Neoadjuvant Treatment Justified in Clinical T1 Pancreatic Ductal Adenocarcinoma?
J. Clin. Med. 2021, 10(4), 873; https://doi.org/10.3390/jcm10040873 - 20 Feb 2021
Viewed by 538
Abstract
Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical [...] Read more.
Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical T1 stage pancreatic cancer. Methods: Data from two centers were included in the comparative analysis, with overall and recurrence-free survival as primary outcomes, between January 2010 and December 2017. Results: In total, 45 patients were retrospectively reviewed in this study. Two patients in the neoadjuvant group were excluded because of distant metastasis during neoadjuvant treatment. Finally, 43 patients underwent a pancreatectomy for clinical T1 pancreatic cancer, of whom, 35 and 8 patients underwent upfront surgery and neoadjuvant treatment, respectively. Overall survival was similar in the two study groups (5-year overall survival rate: neoadjuvant group, 75%; upfront surgery group, 43.9%, p = 0.066). Conclusions: In our study on patients with clinical T1 stage pancreatic cancer, no significant differences were reported in the oncological outcome in the neoadjuvant therapy group. Large-scale prospective studies are needed to determine the survival benefits of neoadjuvant treatment for early-stage pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessArticle
Comparison of Preoperative Evaluation with the Pathological Report in Intraductal Papillary Mucinous Neoplasms: A Single-Center Experience
J. Clin. Med. 2021, 10(4), 678; https://doi.org/10.3390/jcm10040678 - 10 Feb 2021
Viewed by 408
Abstract
The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study [...] Read more.
The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
Open AccessArticle
Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer
J. Clin. Med. 2021, 10(3), 490; https://doi.org/10.3390/jcm10030490 - 30 Jan 2021
Viewed by 722
Abstract
B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of [...] Read more.
B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessArticle
Risk of Developing Pancreatic Cancer in Patients with Chronic Pancreatitis
J. Clin. Med. 2020, 9(11), 3720; https://doi.org/10.3390/jcm9113720 - 19 Nov 2020
Viewed by 631
Abstract
Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected [...] Read more.
Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected data of patients with CP was performed. Aetiology of CP was determined according to the M-ANNHEIM classification system and only patients with definite CP > 18 years at data analysis were included. The final dataset included 581 patients with definite CP diagnosed between 2003 and 2018. Results: At CP diagnosis, there were 371 (63.9%) males and 210 (36.1%) females (median age 57 years, range 2–86). During 3423 person-years of observation, six pancreatic cancers were diagnosed (0.2% year). The mean time between diagnosis of CP and the occurrence of PDAC was 5.0 years (range 2.7–8.6). None of the cancer patients had a family history of PDAC. Diabetes mellitus (DM) was present in five of six (83.3%) patients with PDAC: in three patients before and in two after CP diagnosis. Clinical/laboratory signs of pancreatic exocrine insufficiency (PEI) were present in five of six (83.3%) patients with PDAC: in two at diagnosis of CP and in three after diagnosis. The mean survival time was 4 months after the diagnosis of PDAC (range 0.5–13). PDAC occurred significantly more often (p < 0.001) in two groups of patients without previous acute pancreatitis (AP): 2 of 20 patients (10%) with low body mass index (BMI) and PEI and in 3 of 10 (30%) patients with high BMI and DM at diagnosis of CP. Conclusions: Patients with CP have a high risk of developing PDAC, although risk is low in absolute terms. Our data suggest the possibility of defining subgroups of patients with a particularly elevated risk of PDAC. Such a possibility would open a path to personalised decision making on initiation of PDAC surveillance of patients with no previous episode of AP, (i) with low BMI and PEI, or (ii) elevated BMI and DM. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessArticle
Survival Outcomes of Pancreatic Intraepithelial Neoplasm (PanIN) versus Intraductal Papillary Mucinous Neoplasm (IPMN) Associated Pancreatic Adenocarcinoma
J. Clin. Med. 2020, 9(10), 3102; https://doi.org/10.3390/jcm9103102 - 25 Sep 2020
Cited by 2 | Viewed by 679
Abstract
Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with survival rate and prognosis are lacking. We retrospectively evaluated 72 pancreatic adenocarcinoma tumor resection patients at the University of Kansas [...] Read more.
Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with survival rate and prognosis are lacking. We retrospectively evaluated 72 pancreatic adenocarcinoma tumor resection patients at the University of Kansas Hospital between August 2009 and March 2019. Patients were divided into one of two groups, PanIN or IPMN, based on the results of the surgical pathology report. We compared baseline characteristics, overall survival (OS), and progression free survival (PFS) between the two groups, as well as OS and PFS based on local or distant tumor recurrence for both groups combined. 52 patients had PanINs and 20 patients had IPMNs. Patients who had an IPMN precursor lesion had better median PFS and OS when compared to patients with PanIN precursor lesions. However, the location of tumor recurrence (local or distant) did not show a statistically significant difference in OS. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessArticle
Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis
J. Clin. Med. 2020, 9(7), 2132; https://doi.org/10.3390/jcm9072132 - 06 Jul 2020
Cited by 1 | Viewed by 883
Abstract
Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review [...] Read more.
Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs. 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Review

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Open AccessReview
Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies
J. Clin. Med. 2021, 10(8), 1665; https://doi.org/10.3390/jcm10081665 - 13 Apr 2021
Viewed by 268
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence [...] Read more.
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals’ risk for PCa. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessReview
Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy
J. Clin. Med. 2021, 10(8), 1609; https://doi.org/10.3390/jcm10081609 - 10 Apr 2021
Viewed by 233
Abstract
Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of [...] Read more.
Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessReview
A Review of the Diagnosis and Management of Premalignant Pancreatic Cystic Lesions
J. Clin. Med. 2021, 10(6), 1284; https://doi.org/10.3390/jcm10061284 - 19 Mar 2021
Viewed by 382
Abstract
Pancreatic cystic lesions are an increasingly common clinical finding. They represent a heterogeneous group of lesions that include two of the three known precursors of pancreatic cancer, intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). Given that approximately 8% of pancreatic [...] Read more.
Pancreatic cystic lesions are an increasingly common clinical finding. They represent a heterogeneous group of lesions that include two of the three known precursors of pancreatic cancer, intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). Given that approximately 8% of pancreatic cancers arise from these lesions, careful surveillance and timely surgery offers an opportunity for early curative resection in a disease with a dismal prognosis. This review summarizes the current evidence and guidelines for the diagnosis and management of IPMN/MCN. Current pre-operative diagnostic tests in pancreatic cysts are imperfect and a proportion of patients continue to undergo unnecessary surgical resection annually. Balancing cancer prevention while preventing surgical overtreatment, continues to be challenging when managing pancreatic cysts. Cyst fluid molecular markers, such as KRAS, GNAS, VHL, PIK3CA, SMAD4 and TP53, as well as emerging endoscopic technologies such as needle-based confocal laser endomicroscopy and through the needle microbiopsy forceps demonstrate improved diagnostic accuracy. Differences in management and areas of uncertainty between the guidelines are also discussed, including indications for surgery, surveillance protocols and if and when surveillance can be discontinued. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
Open AccessReview
Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography
J. Clin. Med. 2021, 10(6), 1151; https://doi.org/10.3390/jcm10061151 - 10 Mar 2021
Viewed by 650
Abstract
Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult [...] Read more.
Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessReview
The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies
J. Clin. Med. 2021, 10(4), 566; https://doi.org/10.3390/jcm10040566 - 03 Feb 2021
Viewed by 829
Abstract
Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or [...] Read more.
Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessReview
Molecular and Metabolic Subtypes Correspondence for Pancreatic Ductal Adenocarcinoma Classification
J. Clin. Med. 2020, 9(12), 4128; https://doi.org/10.3390/jcm9124128 - 21 Dec 2020
Viewed by 1150
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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