-
1.
Harnessing metabolic dependencies in pancreatic cancers.
Encarnación-Rosado, J, Kimmelman, AC
Nature reviews. Gastroenterology & hepatology. 2021;(7):482-492
-
-
Free full text
-
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a 5-year survival rate of <10%. The tumour microenvironment (TME) of PDAC is characterized by excessive fibrosis and deposition of extracellular matrix, termed desmoplasia. This unique TME leads to high interstitial pressure, vascular collapse and low nutrient and oxygen diffusion. Together, these factors contribute to the unique biology and therapeutic resistance of this deadly tumour. To thrive in this hostile environment, PDAC cells adapt by using non-canonical metabolic pathways and rely on metabolic scavenging pathways such as autophagy and macropinocytosis. Here, we review the metabolic pathways that PDAC use to support their growth in the setting of an austere TME. Understanding how PDAC tumours rewire their metabolism and use scavenging pathways under environmental stressors might enable the identification of novel therapeutic approaches.
-
2.
Early Detection of Pancreatic Cancer: Applying Artificial Intelligence to Electronic Health Records.
Kenner, BJ, Abrams, ND, Chari, ST, Field, BF, Goldberg, AE, Hoos, WA, Klimstra, DS, Rothschild, LJ, Srivastava, S, Young, MR, et al
Pancreas. 2021;(7):916-922
-
-
Free full text
-
Abstract
The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: "Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)" in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.
-
3.
Nutritional considerations for the management of the older person with hepato-pancreatico-biliary malignancy.
Bibby, N, Griffin, O
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):533-538
Abstract
Malnutrition and cancer cachexia are prevalent in older people with hepato-pancreatico-biliary (HPB) malignancy, with the resultant loss of muscle mass and function accelerating normal age-associated losses. Unintentional weight loss may be missed in patients with pre-illness obesity, delaying diagnosis and limiting treatment potential and access. Sarcopenia and/or sarcopenic obesity increase the risk of dose-limiting chemotherapy toxicity, post-operative mortality and overall survival. The aetiology of malnutrition and weight loss is multi-factorial in patients with HPB malignancy, necessitating systematic evaluation of endocrine and exocrine function, and multi-modal therapeutic strategies. Prehabilitation aims to reduce the complications and side effects associated with treatment, aid recovery and improve quality of life, with the greatest benefits potentially being seen in high risk groups, such as people who are older and frail. Post-operatively, individualised nutritional support therapies targeting the preservation of weight and muscle indices are required to improve post-operative morbidity, and avoid delay or early cessation of any necessary adjuvant therapy.
-
4.
Store-Operated Calcium Entry: Shaping the Transcriptional and Epigenetic Landscape in Pancreatic Cancer.
Kutschat, AP, Johnsen, SA, Hamdan, FH
Cells. 2021;(5)
Abstract
Pancreatic ductal adenocarcinoma (PDAC) displays a particularly poor prognosis and low survival rate, mainly due to late diagnosis and high incidence of chemotherapy resistance. Genomic aberrations, together with changes in the epigenomic profile, elicit a shift in cellular signaling response and a transcriptional reprograming in pancreatic tumors. This endows them with malignant attributes that enable them to not only overcome chemotherapeutic challenges, but to also attain diverse oncogenic properties. In fact, certain genetic amplifications elicit a rewiring of calcium signaling, which can confer ER stress resistance to tumors while also aberrantly activating known drivers of oncogenic programs such as NFAT. While calcium is a well-known second messenger, the transcriptional programs driven by aberrant calcium signaling remain largely undescribed in pancreatic cancer. In this review, we focus on calcium-dependent signaling and its role in epigenetic programs and transcriptional regulation. We also briefly discuss genetic aberration events, exemplifying how genetic alterations can rewire cellular signaling cascades, including calcium-dependent ones.
-
5.
New Roles for Vitamin D Superagonists: From COVID to Cancer.
Easty, DJ, Farr, CJ, Hennessy, BT
Frontiers in endocrinology. 2021;:644298
Abstract
Vitamin D is a potent steroid hormone that induces widespread changes in gene expression and controls key biological pathways. Here we review pathophysiology of vitamin D with particular reference to COVID-19 and pancreatic cancer. Utility as a therapeutic agent is limited by hypercalcemic effects and attempts to circumvent this problem have used vitamin D superagonists, with increased efficacy and reduced calcemic effect. A further caveat is that vitamin D mediates multiple diverse effects. Some of these (anti-fibrosis) are likely beneficial in patients with COVID-19 and pancreatic cancer, whereas others (reduced immunity), may be beneficial through attenuation of the cytokine storm in patients with advanced COVID-19, but detrimental in pancreatic cancer. Vitamin D superagonists represent an untapped resource for development of effective therapeutic agents. However, to be successful this approach will require agonists with high cell-tissue specificity.
-
6.
Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.
Sobocki, BK, Kaźmierczak-Siedlecka, K, Folwarski, M, Hawryłkowicz, V, Makarewicz, W, Stachowska, E
Nutrients. 2021;(12)
Abstract
Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.
-
7.
The Human Microbiomes in Pancreatic Cancer: Towards Evidence-Based Manipulation Strategies?
Brandi, G, Turroni, S, McAllister, F, Frega, G
International journal of molecular sciences. 2021;(18)
Abstract
Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic "hub" interfaced between the gut and the host.
-
8.
Frailty assessment tools and geriatric assessment in older patients with hepatobiliary and pancreatic malignancies.
Rostoft, S, van Leeuwen, B
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):514-518
Abstract
BACKGROUND The majority of patients with hepatobiliary and pancreatic (HBP) malignancies are older than 65 years. Due to the heterogeneity of this older population, decisions regarding surgical treatment cannot rely solely on treatment guidelines, but have to take into account patient frailty, geriatric impairments and resilience as well as patient preferences. In the few studies of older patients with HBP malignancies that have included a preoperative geriatric assessment (GA), frailty and elements from the GA such as reduced functional status have emerged as powerful predictors of postoperative morbidity and mortality, length of stay, type of treatment received and survival. A GA is a systematic evaluation of functional status, comorbidities, polypharmacy, cognition, nutritional status, emotional status, and social support. MATERIALS AND METHODS A Pubmed search identifying clinical studies investigating the association between frailty, GA and outcomes in patients with HBP malignancies. RESULTS A total of 20 studies were included in this review. For HBP malignancies, the evidence linking frailty and GA variables to negative outcomes is limited, but generally shows that frailty, functional dependency, comorbidity, and sarcopenia predict postoperative complications and survival. CONCLUSION Although scarcely investigated, frailty and elements from a GA seem to be associated with negative short- and long-term treatment outcomes in older patients with HBP malignancies. Future studies should investigate the impact of geriatric interventions and prehabilitation on outcomes.
-
9.
Natural Products for Pancreatic Cancer Treatment: From Traditional Medicine to Modern Drug Discovery.
Kim, A, Ha, J, Kim, J, Cho, Y, Ahn, J, Cheon, C, Kim, SH, Ko, SG, Kim, B
Nutrients. 2021;(11)
Abstract
Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.
-
10.
Enhanced recovery after surgery programmes in older patients undergoing hepatopancreatobiliary surgery: what benefits might prehabilitation have?
Bongers, BC, Dejong, CHC, den Dulk, M
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(3 Pt A):551-559
Abstract
Due to an aging population and the related growing number of less physically fit patients with multiple comorbidities, adequate perioperative care is a new and rapidly developing clinical science that is becoming increasingly important. This narrative review focuses on enhanced recovery after surgery (ERAS®) programmes and the growing interest in prehabilitation programmes to improve patient- and treatment-related outcomes in older patients undergoing hepatopancreatobiliary (HPB) surgery. Future steps required in the further development of optimal perioperative care in HPB surgery are also discussed. Multidisciplinary preoperative risk assessment in multiple domains should be performed to identify, discuss, and reduce risks for optimal outcomes, or to consider alternative treatment options. Prehabilitation should focus on high-risk patients based on evidence-based cut-off values and should aim for (partly) supervised multimodal prehabilitation tailored to the individual patient's risk factors. The program should be executed in the living context of these high-risk patients to improve the participation rate and adherence, as well as to involve the patient's informal support system. Developing tailored (multimodal) prehabilitation programmes for the right patients, in the right context, and using the right outcome measures is important to demonstrate its potential to further improve patient- and treatment-related outcomes following HPB surgery.