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Cancers
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Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment
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Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment

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

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 30047

Special Issue Editor

Prof. Dr. Andrzej Deptała

E-Mail Website
Guest Editor
Department of Cancer Prevention, Medical University of Warsaw, Warsaw, Poland
Interests: pancreatic cancer; colorectal cancer; hepatocellular cancer

Special Issue Information

Dear Colleagues,

Therapy of pancreatic cancer is progressing slowly but step by step. Surgery remains the potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC) without metastases, and en bloc resection with adequate surgical margins is associated with long-term survival. Venous invasion does not preclude patients from surgery because combined venous resection and reconstitution can be safely performed. Resection and reconstitution of the affected arteries have been recently reported without a significant increase in mortality. Despite advanced surgery, most patients will develop metastatic disease and there is therefore a great deal of debate about how to improve patient survival by using neoadjuvant or adjuvant chemotherapy with or without radiation therapy. Optimal supportive management, in particular nutritional treatment and care for a good quality of life of patients with PDAC, play currently an increasingly important role. In the age of molecularly-targeted drugs and immunotherapy, researchers put great efforts based on genomics and proteomics of PDAC into finding the best targeted therapy. Using our own many years of experience in the treatment of patients with PDAC and taking into account the latest scientific achievements, this Special Issue will discuss recent development in understanding genomic characteristics, early detection approach, innovations in the treatment of resectable, borderline resectable, locally advanced and metastatic PDAC, and in application of the therapeutics targeting new targets in pancreatic carcinoma.

Prof. Dr. Andrzej Deptała
Guest Editor

Manuscript Submission Information

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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
  • pancreatic ductal adenocarcinoma
  • genetic changes
  • genomics
  • surgical resection
  • radiotherapy
  • radiochemotherapy
  • chemotherapy
  • targeted therapy
  • immunotherapy
  • resectable tumor
  • borderline resectable tumor
  • metastatic disease
  • nutritional treatment
  • quality of life

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Published Papers (10 papers)

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Research

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24 pages, 2251 KiB  
Article
Serum Metabolite Biomarkers for Pancreatic Tumors: Neuroendocrine and Pancreatic Ductal Adenocarcinomas—A Preliminary Study
by Karolina Skubisz, Krzysztof Dąbkowski, Emilia Samborowska, Teresa Starzyńska, Anna Deskur, Filip Ambrozkiewicz, Jakub Karczmarski, Mariusz Radkiewicz, Katarzyna Kusnierz, Beata Kos-Kudła, Tadeusz Sulikowski, Patrycja Cybula and Agnieszka Paziewska
Cancers 2023, 15(12), 3242; https://doi.org/10.3390/cancers15123242 - 19 Jun 2023
Cited by 2 | Viewed by 2224
Abstract
Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal [...] Read more.
Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET. Methods: Using the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography–mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients. Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients (p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = −1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86. Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients’ condition, helping with pharmacological treatment or dietary strategies. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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Review

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14 pages, 1109 KiB  
Review
How A Patient with Resectable or Borderline Resectable Pancreatic Cancer should Be Treated—A Comprehensive Review
by Daria Kwaśniewska, Marta Fudalej, Paweł Nurzyński, Anna Badowska-Kozakiewicz, Aleksandra Czerw, Elżbieta Cipora, Katarzyna Sygit, Ewa Bandurska and Andrzej Deptała
Cancers 2023, 15(17), 4275; https://doi.org/10.3390/cancers15174275 - 26 Aug 2023
Cited by 2 | Viewed by 2161
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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17 pages, 321 KiB  
Review
Evaluation of Nutritional Status and the Impact of Nutritional Treatment in Patients with Pancreatic Cancer
by Dominika Mękal, Jacek Sobocki, Anna Badowska-Kozakiewicz, Katarzyna Sygit, Elżbieta Cipora, Ewa Bandurska, Aleksandra Czerw and Andrzej Deptała
Cancers 2023, 15(15), 3816; https://doi.org/10.3390/cancers15153816 - 27 Jul 2023
Cited by 5 | Viewed by 2771
Abstract
Patients with pancreatic cancer who develop irreversible cancer cachexia have a life expectancy of less than 3 months. Therefore, it is extremely important to evaluate the patient’s nutritional status as early as possible and to implement an appropriate nutritional intervention in order to [...] Read more.
Patients with pancreatic cancer who develop irreversible cancer cachexia have a life expectancy of less than 3 months. Therefore, it is extremely important to evaluate the patient’s nutritional status as early as possible and to implement an appropriate nutritional intervention in order to reduce the risk of further weight loss and/or muscle loss, which affect the outcomes of cancer treatment and the correct nutritional treatment in patients with pancreatic cancer. A literature review was performed by using the PubMed and Cochrane quick search methodology. The main purpose of this review was to present the current approach to nutritional treatment in pancreatic cancer. The review included publications, most of which concerned clinical nutrition as part of the phase of treatment of patients with pancreatic cancer, nutritional and metabolic disorders in pancreatic cancer, and the period after pancreatic resection. Some of the publications concerned various nutritional interventions in patients with pancreatic cancer undergoing chemotherapy or surgical treatment (nutritional support before surgery, after surgery, or during palliative treatment). There is an unmet need for integrated nutritional therapy as a key part of the comprehensive care process for PC patients. Nutritional counseling is the first line of nutritional treatment for malnourished cancer patients, but pancreatic enzyme replacement therapy also constitutes the cornerstone of nutritional treatment for relieving symptoms of indigestion and maintaining or improving nutritional status. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
11 pages, 586 KiB  
Review
Overview of Pancreatic Cancer Epidemiology in Europe and Recommendations for Screening in High-Risk Populations
by Olga Partyka, Monika Pajewska, Daria Kwaśniewska, Aleksandra Czerw, Andrzej Deptała, Michał Budzik, Elżbieta Cipora, Izabela Gąska, Lucyna Gazdowicz, Aneta Mielnik, Katarzyna Sygit, Marian Sygit, Edyta Krzych-Fałta, Daria Schneider-Matyka, Szymon Grochans, Anna M. Cybulska, Jarosław Drobnik, Ewa Bandurska, Weronika Ciećko, Piotr Ratajczak, Karolina Kamecka, Michał Marczak and Remigiusz Kozłowskiadd Show full author list remove Hide full author list
Cancers 2023, 15(14), 3634; https://doi.org/10.3390/cancers15143634 - 15 Jul 2023
Cited by 20 | Viewed by 5680
Abstract
Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results [...] Read more.
Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results of observational studies on patients with pancreatic cancer and people from high-risk groups was used to summarize the knowledge on risk factors. The GLOBOCAN 2020 data were used to assess the epidemiological situation in Europe. A summary of screening recommendations was prepared based on the available documents from medical organizations and associations. Pancreatic cancer risk factors are divided into two main groups: non-modifiable factors, e.g., hereditary factors and age, which increase the risk of developing this disease, and modifiable factors—BMI, smoking, and alcohol consumption. Hereditary factors account for 10% of pancreatic cancer cases. The highly specialized methods of early detection, (MRI, CT, or EUS) are used for screening high-risk populations. Of all the imaging methods, EUS is considered the most sensitive for pancreatic cancer and allows an accurate assessment of the size of even small lesions (<30 mm) and the extent of tumour infiltration into blood vessels. The available studies vary on the level of sensitivity and specificity of these methods for the diagnosis of pancreatic cancer. EUS, MRI, and CT are also expensive procedures and in some patients can be invasive, which is one of the arguments against the introduction of population screening programs based on imaging methods. Therefore, it is important to look for viable solutions that would improve early detection. This is important from the point of view of healthcare systems in Europe, where almost 29% of all global pancreatic cancer cases are reported. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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13 pages, 296 KiB  
Review
Radiotherapy in Pancreatic Cancer: To Whom, When, and How?
by Michał Falco, Bartłomiej Masojć and Tadeusz Sulikowski
Cancers 2023, 15(13), 3382; https://doi.org/10.3390/cancers15133382 - 28 Jun 2023
Cited by 9 | Viewed by 1638
Abstract
The diagnosis rate of pancreatic cancer is steadily increasing. The average age of onset is close to 70 years. In most cases, the disease is diagnosed at an advanced stage. The indications for and techniques of radiotherapy are changing over time. The aim [...] Read more.
The diagnosis rate of pancreatic cancer is steadily increasing. The average age of onset is close to 70 years. In most cases, the disease is diagnosed at an advanced stage. The indications for and techniques of radiotherapy are changing over time. The aim of this thesis is to present the role and possibilities of radiotherapy from the perspective of radiation oncologist. The most common cause of treatment failure in pancreatic cancer remains generalisation. The implementation of new systemic treatment regimens contributes to improved treatment outcomes regardless of the stage of the disease. With improved treatment outcomes in terms of the incidence of distant metastases, the impact of local curability on the length and quality of life of patients increases. Modern radiotherapy offers the opportunity to achieve high local cure rates. Postoperative radiotherapy in combination with chemotherapy seems justified in the group of postoperative pancreatic cancer patients with pT3 and pN+ features. In the group of patients with borderline resectable pancreatic cancer, the impact of radiotherapy in combination with the latest chemotherapy regimens is difficult to define clearly. In the setting of a diagnosis of advanced pancreatic cancer, radiotherapy, especially stereotactic radiotherapy, in combination with chemotherapy, contributes to improved local curability and allows to achieve a significantly reduced level of pain. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
15 pages, 1626 KiB  
Review
Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma
by Maciej Słodkowski, Marek Wroński, Dominika Karkocha, Leszek Kraj, Kaja Śmigielska and Aneta Jachnis
Cancers 2023, 15(9), 2584; https://doi.org/10.3390/cancers15092584 - 30 Apr 2023
Cited by 8 | Viewed by 2451
Abstract
Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for [...] Read more.
Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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18 pages, 981 KiB  
Review
New Treatment Options in Metastatic Pancreatic Cancer
by Marta Fudalej, Daria Kwaśniewska, Paweł Nurzyński, Anna Badowska-Kozakiewicz, Dominika Mękal, Aleksandra Czerw, Katarzyna Sygit and Andrzej Deptała
Cancers 2023, 15(8), 2327; https://doi.org/10.3390/cancers15082327 - 17 Apr 2023
Cited by 7 | Viewed by 2485
Abstract
Pancreatic cancer (PC) is the seventh leading cause of cancer death across the world. Poor prognosis of PC is associated with several factors, such as diagnosis at an advanced stage, early distant metastases, and remarkable resistance to most conventional treatment options. The pathogenesis [...] Read more.
Pancreatic cancer (PC) is the seventh leading cause of cancer death across the world. Poor prognosis of PC is associated with several factors, such as diagnosis at an advanced stage, early distant metastases, and remarkable resistance to most conventional treatment options. The pathogenesis of PC seems to be significantly more complicated than originally assumed, and findings in other solid tumours cannot be extrapolated to this malignancy. To develop effective treatment schemes prolonging patient survival, a multidirectional approach encompassing different aspects of the cancer is needed. Particular directions have been established; however, further studies bringing them all together and connecting the strengths of each therapy are needed. This review summarises the current literature and provides an overview of new or emerging therapeutic strategies for the more effective management of metastatic PC. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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19 pages, 593 KiB  
Review
Rare Non-Neuroendocrine Pancreatic Tumours
by Agata Mormul, Emilia Włoszek, Julia Nowoszewska, Marta Fudalej, Michał Budzik, Anna Badowska-Kozakiewicz and Andrzej Deptała
Cancers 2023, 15(8), 2216; https://doi.org/10.3390/cancers15082216 - 9 Apr 2023
Cited by 3 | Viewed by 2317
Abstract
The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and [...] Read more.
The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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11 pages, 629 KiB  
Review
Treatment Costs and Social Burden of Pancreatic Cancer
by Elżbieta Cipora, Olga Partyka, Monika Pajewska, Aleksandra Czerw, Katarzyna Sygit, Marian Sygit, Mateusz Kaczmarski, Dominika Mękal, Edyta Krzych-Fałta, Anna Jurczak, Katarzyna Karakiewicz-Krawczyk, Sylwia Wieder-Huszla, Tomasz Banaś, Ewa Bandurska, Weronika Ciećko and Andrzej Deptała
Cancers 2023, 15(6), 1911; https://doi.org/10.3390/cancers15061911 - 22 Mar 2023
Cited by 6 | Viewed by 3280
Abstract
(1) Background: Pancreatic cancer is the cancer with the third-highest mortality rate, and forecasts indicate its growing share in morbidity. The basis of treatment is inpatient chemotherapy and there is a strong focus on palliative care. (2) Methods: A literature review was conducted [...] Read more.
(1) Background: Pancreatic cancer is the cancer with the third-highest mortality rate, and forecasts indicate its growing share in morbidity. The basis of treatment is inpatient chemotherapy and there is a strong focus on palliative care. (2) Methods: A literature review was conducted based on the rapid review methodology in PubMed and Cochrane databases. The search was supplemented with publications from the snowball search. Qualitative assessment of included publications was performed using AMSTAR2 modified scheme. (3) Results: The review included 17 publications, of which majority concerned direct costs related to the adopted treatment regimen. Most of the publications focused on comparing the cost-effectiveness of drug therapies and the costs of palliative treatment. Other publications concerned indirect costs generated by pancreatic cancer. They particularly focused on the economic burden of lost productivity due to sickness absence. (4) Conclusion: The increase in the incidence of pancreatic cancer translates into an increase in the costs of the health care system and indirect costs. Due to the significant share of hospitalization in the health care structure, direct costs are increasing. The inpatient treatment regimen and side effects translate into a loss of productivity for patients with pancreatic cancer. Among gastrointestinal cancers, pancreatic cancer generates the second largest indirect costs, although it has a much lower incidence rate than the dominant colorectal cancer. This indicates a significant problem of the economic burden of this cancer. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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22 pages, 434 KiB  
Review
Genetics, Genomics and Emerging Molecular Therapies of Pancreatic Cancer
by Jakub Liu, Magdalena Mroczek, Anna Mach, Maria Stępień, Angelika Aplas, Bartosz Pronobis-Szczylik, Szymon Bukowski, Magda Mielczarek, Ewelina Gajewska, Piotr Topolski, Zbigniew J. Król, Joanna Szyda and Paula Dobosz
Cancers 2023, 15(3), 779; https://doi.org/10.3390/cancers15030779 - 27 Jan 2023
Cited by 8 | Viewed by 4163
Abstract
The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for [...] Read more.
The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for 5 years from the diagnosis, 8% live for 2 years, and almost half live for only about 3 months. A family predisposition to pancreatic cancer occurs in about 10% of cases. Several oncogenes in which somatic changes lead to the development of tumours, including genes BRCA1/2 and PALB2, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, are involved in pancreatic cancer. Between 4% and 10% of individuals with pancreatic cancer will have a mutation in one of these genes. Six percent of patients with pancreatic cancer have NTRK pathogenic fusion. The pathogenesis of pancreatic cancer can in many cases be characterised by homologous recombination deficiency (HRD)—cell inability to effectively repair DNA. It is estimated that from 24% to as many as 44% of pancreatic cancers show HRD. The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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