The role of metabolic ecosystem in cancer progression — metabolic plasticity and mTOR hyperactivity in tumor tissues
AbstractDespite advancements in cancer management, tumor relapse and metastasis are associated with poor outcomes in many cancers. Over the past decade, oncogene-driven carcinogenesis, dysregulated cellular signaling networks, dynamic changes in the tissue microenvironment, epithelial-mesenchymal transitions, protein expression within regulatory pathways, and their part in tumor progression are described in several studies. However, the complexity of metabolic enzyme expression is considerably under evaluated. Alterations in cellular metabolism determine the individual phenotype and behavior of cells, which is a well-recog...
Source: Cancer and Metastasis Reviews - January 14, 2022 Category: Cancer & Oncology Source Type: research

Of vascular defense, hemostasis, cancer, and platelet biology: an evolutionary perspective
AbstractWe have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary in...
Source: Cancer and Metastasis Reviews - January 12, 2022 Category: Cancer & Oncology Source Type: research

Emerging roles of epithelial-mesenchymal plasticity in invasion-metastasis cascade and therapy resistance
AbstractStrong association of cancer incidence and its progression with mortality highlights the need to decipher the cellular and molecular mechanisms that drive tumor cells to rapidly progress to metastatic disease and therapy resistance. Epithelial-mesenchymal plasticity (EMP) emerged as a key regulator of metastatic outgrowth. It allows neoplastic epithelial cells to delaminate from their neighbors either individually or collectively, traverse the extracellular matrix (ECM) barrier, enter into the circulation, and establish distal metastases. Plasticity between epithelial and mesenchymal states and the existence of hyb...
Source: Cancer and Metastasis Reviews - January 3, 2022 Category: Cancer & Oncology Source Type: research

Glycosylation as a regulator of site-specific metastasis
AbstractMetastasis is considered to be responsible for 90% of cancer-related deaths. Although it is clinically evident that metastatic patterns vary by primary tumor type, the molecular mechanisms underlying the site-specific nature of metastasis are an area of active investigation. One mechanism that has emerged as an important player in this process is glycosylation, or the addition of sugar moieties onto protein and lipid substrates. Glycosylation is the most common post-translational modification, occurring on more than 50% of translated proteins. Many of those proteins are either secreted or expressed on the cell memb...
Source: Cancer and Metastasis Reviews - December 30, 2021 Category: Cancer & Oncology Source Type: research

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer
AbstractBreast cancer, the most frequent cancer in women, is characterized by pathological changes to the microbiome of breast tissue, the tumor, the gut, and the urinary tract. Changes to the microbiome are determined by the stage, grade, origin (NST/lobular), and receptor status of the tumor. This year is the 50th anniversary of when Hill and colleagues first showed that changes to the gut microbiome can support breast cancer growth, namely that the oncobiome can reactivate excreted estrogens. The currently available human and murine data suggest that oncobiosis is not a cause of breast cancer, but can support its growth...
Source: Cancer and Metastasis Reviews - December 30, 2021 Category: Cancer & Oncology Source Type: research

Glycosylation as a regulator of site-specific metastasis
AbstractMetastasis is considered to be responsible for 90% of cancer-related deaths. Although it is clinically evident that metastatic patterns vary by primary tumor type, the molecular mechanisms underlying the site-specific nature of metastasis are an area of active investigation. One mechanism that has emerged as an important player in this process is glycosylation, or the addition of sugar moieties onto protein and lipid substrates. Glycosylation is the most common post-translational modification, occurring on more than 50% of translated proteins. Many of those proteins are either secreted or expressed on the cell memb...
Source: Cancer and Metastasis Reviews - December 30, 2021 Category: Cancer & Oncology Source Type: research

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer
AbstractBreast cancer, the most frequent cancer in women, is characterized by pathological changes to the microbiome of breast tissue, the tumor, the gut, and the urinary tract. Changes to the microbiome are determined by the stage, grade, origin (NST/lobular), and receptor status of the tumor. This year is the 50th anniversary of when Hill and colleagues first showed that changes to the gut microbiome can support breast cancer growth, namely that the oncobiome can reactivate excreted estrogens. The currently available human and murine data suggest that oncobiosis is not a cause of breast cancer, but can support its growth...
Source: Cancer and Metastasis Reviews - December 30, 2021 Category: Cancer & Oncology Source Type: research

Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators?
AbstractBranched-chain amino acids (BCAA) are essential amino acids utilized in anabolic and catabolic metabolism. While extensively studied in obesity and diabetes, recent evidence suggests an important role for BCAA metabolism in cancer. Elevated plasma levels of BCAA are associated with an increased risk of developing pancreatic cancer, namely pancreatic ductal adenocarcinoma (PDAC), a tumor with one of the highest 1-year mortality rates. The dreadful prognosis for PDAC patients could be attributable also to the early and frequent development of cancer cachexia, a fatal host metabolic reprogramming leading to muscle and...
Source: Cancer and Metastasis Reviews - December 28, 2021 Category: Cancer & Oncology Source Type: research

A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients
AbstractSleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
AbstractSmall cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the therapy; however, acquired resistance develops almost in all patients. Although SCLC has been formerly considered a homogeneous disease, recent advances in SCLC research have highlighted the importance of inter- and intratumoral heterogeneity and have resulted in the subclassification of SCLC. The newly described SCLC subtypes are characterized by distinct biological behavior and vulnerabilities that can be therapeutically exploited. The PI3K/Akt/mTOR pat...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

The role of the metabolite cargo of extracellular vesicles in tumor progression
AbstractMetabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived extracellular vesicles (EVs) is still in its infancy. EVs are membrane-bound sacs with a complex molecular composition secreted by all living cells. They are key mediators of intercellular communication both in normal and pathological conditions and play a crucial role in tumor development. Although lipids are major components of EVs, most of the EV cargo studies have targeted proteins and nucleic acids. The potential of the EV metabolome as a source f...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

Model systems in SDHx-related pheochromocytoma/paraganglioma
AbstractPheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. GermlineSDH subunitB (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely ...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients
AbstractSleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations
AbstractSmall cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the therapy; however, acquired resistance develops almost in all patients. Although SCLC has been formerly considered a homogeneous disease, recent advances in SCLC research have highlighted the importance of inter- and intratumoral heterogeneity and have resulted in the subclassification of SCLC. The newly described SCLC subtypes are characterized by distinct biological behavior and vulnerabilities that can be therapeutically exploited. The PI3K/Akt/mTOR pat...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

The role of the metabolite cargo of extracellular vesicles in tumor progression
AbstractMetabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived extracellular vesicles (EVs) is still in its infancy. EVs are membrane-bound sacs with a complex molecular composition secreted by all living cells. They are key mediators of intercellular communication both in normal and pathological conditions and play a crucial role in tumor development. Although lipids are major components of EVs, most of the EV cargo studies have targeted proteins and nucleic acids. The potential of the EV metabolome as a source f...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

Model systems in SDHx-related pheochromocytoma/paraganglioma
AbstractPheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. GermlineSDH subunitB (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely ...
Source: Cancer and Metastasis Reviews - December 27, 2021 Category: Cancer & Oncology Source Type: research

Adipocytokines and disease progression in endometrial cancer: a systematic review
The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF- α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endome...
Source: Cancer and Metastasis Reviews - December 24, 2021 Category: Cancer & Oncology Source Type: research

Extracellular citrate and metabolic adaptations of cancer cells
AbstractIt is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypo...
Source: Cancer and Metastasis Reviews - December 21, 2021 Category: Cancer & Oncology Source Type: research

Tumor metabolism: metabolic alterations and heterogeneity in cancer progression
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - December 16, 2021 Category: Cancer & Oncology Source Type: research

Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets
AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers globally with a mortality rate exceeding 95% and very limited therapeutic options. A hallmark of PDAC is its acidic tumor microenvironment, further characterized by excessive fibrosis and depletion of oxygen and nutrients due to poor vascularity. The combination of PDAC driver mutations and adaptation to this hostile environment drives extensive metabolic reprogramming of the cancer cells toward non-canonical metabolic pathways and increases reliance on scavenging mechanisms such as autophagy and macropinocytosis. In addition, the cancer cells ...
Source: Cancer and Metastasis Reviews - December 2, 2021 Category: Cancer & Oncology Source Type: research

What do cellular responses to acidity tell us about cancer?
AbstractThe notion that invasive cancer is a product of somatic evolution is a well-established theory that can be modelled mathematically and demonstrated empirically from therapeutic responses. Somatic evolution is by no means deterministic, and ample opportunities exist to steer its trajectory towards cancer cell extinction. One such strategy is to alter the chemical microenvironment shared between host and cancer cells in a way that no longer favours the latter. Ever since the first description of the Warburg effect, acidosis has been recognised as a key chemical signature of the tumour microenvironment. Recent finding...
Source: Cancer and Metastasis Reviews - November 30, 2021 Category: Cancer & Oncology Source Type: research

Lipid metabolism reprogramming in renal cell carcinoma
AbstractMetabolic reprogramming is recognized as a hallmark of cancer. Lipids are the essential biomolecules required for membrane biosynthesis, energy storage, and cell signaling. Altered lipid metabolism allows tumor cells to survive in the nutrient-deprived environment. However, lipid metabolism remodeling in renal cell carcinoma (RCC) has not received the same attention as in other cancers. RCC, the most common type of kidney cancer, is associated with almost 15,000 death in the USA annually. Being refractory to conventional chemotherapy agents and limited available targeted therapy options has made the treatment of me...
Source: Cancer and Metastasis Reviews - November 6, 2021 Category: Cancer & Oncology Source Type: research

Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology
ConclusionsOur systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - October 30, 2021 Category: Cancer & Oncology Source Type: research

Glioma: molecular signature and crossroads with tumor microenvironment
AbstractIn patients with glioblastoma, the average survival time with current treatments is short, mainly due to recurrences and resistance to therapy. This insufficient treatment success is, in large parts, due to the tremendous molecular heterogeneity of gliomas, which affects the overall prognosis and response to therapies and plays a vital role in gliomas ’ grading. In addition, the tumor microenvironment is a major player for glioma development and resistance to therapy. Active communication between glioma cells and local or neighboring healthy cells and the immune environment promotes the cancerogenic processes...
Source: Cancer and Metastasis Reviews - October 23, 2021 Category: Cancer & Oncology Source Type: research

Debris-stimulated tumor growth: a Pandora ’s box?
AbstractCurrent cancer therapies aim at eradicating cancer cells from the body. However, killing cells generates cell “debris” which can promote tumor progression. Thus, therapy can be a double-edged sword. Specifically, injury and debris generated by cancer therapies, including chemotherapy, radiation, and surgery, may offset their benefit by promoting the secretion of pro-tumorigenic factors (e.g., eicosanoid -driven cytokines) that stimulate regrowth and metastasis of surviving cells. The debris produced by cytotoxic cancer therapy can also contribute to a tumor microenvironment that promotes tumor progressi...
Source: Cancer and Metastasis Reviews - October 19, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - October 19, 2021 Category: Cancer & Oncology Source Type: research

The emerging roles of circular RNAs in vessel co-option and vasculogenic mimicry: clinical insights for anti-angiogenic therapy in cancers
AbstractUnexpected resistance to anti-angiogenic treatment prompted the investigation of non-angiogenic tumor processes. Vessel co-option (VC) and vasculogenic mimicry (VM) are recognized as primary non-angiogenic mechanisms. In VC, cancer cells utilize pre-existing blood vessels for support, whereas in VM, cancer cells channel and provide blood flow to rapidly growing tumors. Both processes have been implicated in the development of tumor and resistance to anti-angiogenic drugs in many tumor types. The morphology, but rare molecular alterations have been investigated in VC and VM. There is a pressing need to better unders...
Source: Cancer and Metastasis Reviews - October 18, 2021 Category: Cancer & Oncology Source Type: research

Updates and new directions in the use of radiation therapy for the treatment of pancreatic adenocarcinoma: dose, sensitization, and novel technology
AbstractPanc reatic ductal adenocarcinoma (PDAC) is a devastating malignancy. There have been few advances that have substantially improved overall survival in the past several years. On its current trajectory, the deaths from PDAC are expected to cross that from all gastrointestinal cancers combined by 2030. Radiation therapy is a technically very complex modality that bridges multiple different treatment strategies. It represents a hybrid among advanced diagnostic imaging, local (often ablative) intervention, and heterogeneous biological mechanisms contributing to normal and oncologic cell kill. In this article, we bri...
Source: Cancer and Metastasis Reviews - October 6, 2021 Category: Cancer & Oncology Source Type: research

Pancreatic cancer: why we must be optimistic?
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - October 6, 2021 Category: Cancer & Oncology Source Type: research

Implications of prognosis-associated genes in pancreatic tumor metastasis: lessons from global studies in bioinformatics
AbstractPancreatic cancer (PC) is a highly lethal malignancy with a 5-year survival rate of 10%. The occurrence of metastasis, among other hallmarks, is the main contributor to its poor prognosis. Consequently, the elucidation of metastatic genes involved in the aggressive nature of the disease and its poor prognosis will result in the development of new treatment modalities for improved management of PC. There is a deep interest in understanding underlying disease pathology, identifying key prognostic genes, and genes associated with metastasis. Computational approaches, which have become increasingly relevant over the la...
Source: Cancer and Metastasis Reviews - September 30, 2021 Category: Cancer & Oncology Source Type: research

Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance
AbstractTo date, the use of immune checkpoint inhibitors has proven largely ineffective in patients with advanced pancreatic ductal adenocarcinoma. A combination of low tumor antigenicity, deficits in immune activation along with an exclusive and suppressive tumor microenvironment result in resistance to host defensives. However, a deepening understanding of these immune escape and suppressive mechanisms has led to the discovery of novel molecular targets and treatment strategies that may hold the key to a long-awaited therapeutic breakthrough. In this review, we describe the tumor-intrinsic and microenvironmental barriers...
Source: Cancer and Metastasis Reviews - September 30, 2021 Category: Cancer & Oncology Source Type: research

Role of non-coding RNAs in tumor progression and metastasis in pancreatic cancer
AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer with an overall 5-year survival rate of less than 10%. The 1-year survival rate of patients with locally advanced or metastatic disease is abysmal. The aggressive nature of cancer cells, hypovascularization, extensive desmoplastic stroma, and immunosuppressive tumor microenvironment (TME) endows PDAC tumors with multiple mechanisms of drug resistance. With no obvious genetic mutation(s) driving tumor progression or metastatic transition, the challenges for understanding the biological mechanism(s) of these processes are paramount. A b...
Source: Cancer and Metastasis Reviews - September 30, 2021 Category: Cancer & Oncology Source Type: research

The tumor microenvironment in pancreatic ductal adenocarcinoma: current perspectives and future directions
AbstractPancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies and is characterized by a unique tumor microenvironment (TME) consisting of an abundant stromal component. Many features contained with the PDAC stroma contribute to resistance to cytotoxic and immunotherapeutic regimens, as well as the propensity for this tumor to metastasize. At the cellular level, PDAC cells crosstalk with a complex mixture of non-neoplastic cell types including fibroblasts, endothelial cells, and immune cells. These intricate interactions fuel the progression and therapeutic resistance of this aggressive cancer. Moreo...
Source: Cancer and Metastasis Reviews - September 30, 2021 Category: Cancer & Oncology Source Type: research

Where is Waldo? or find the platelet
AbstractPlatelets evolved from nucleated thrombocytes that exhibit both coagulation and immune function. The essential role of platelets in coagulation is common knowledge. The larger and critical role of platelets in immune responses and cancer are frequently overlooked in our modern-day, large-data-set, sequencing-oriented efforts. Much like Waldo, their small size, biophysical characteristics, rapid biological responses, active cytoskeleton, migration capacity, and lack of a nucleus make them difficult to track as single platelets disappear while executing their function into the histologic “tissue scape”. T...
Source: Cancer and Metastasis Reviews - September 30, 2021 Category: Cancer & Oncology Source Type: research

MicroRNAs as a clue to overcome breast cancer treatment resistance
AbstractBreast cancer is the most frequent cancer in women worldwide. Despite the improvement in diagnosis and treatments, the rates of cancer relapse and resistance to therapies remain higher than desirable. Alterations in microRNAs have been linked to changes in critical processes related to cancer development and progression. Their involvement in resistance or sensitivity to breast cancer treatments has been documented by differentin vivo andin vitro experiments. The most significant microRNAs implicated in modulating resistance to breast cancer therapies are summarized in this review. Resistance to therapy has been lin...
Source: Cancer and Metastasis Reviews - September 15, 2021 Category: Cancer & Oncology Source Type: research

Multiprong control of glioblastoma multiforme invasiveness: blockade of pro-inflammatory signaling, anti-angiogenesis, and homeostasis restoration
AbstractGlioblastoma multiforme (GBM) is the most invasive type of glial tumor with poor overall survival, despite advances in surgical resection, chemotherapy, and radiation. One of the main challenges in treating GBM is related to the tumor ’s location, complex and heterogeneous biology, and high invasiveness. To meet the demand for oxygen and nutrients, growing tumors induce new blood vessels growth. Antibodies directed against vascular endothelial growth factor (VEGF), which promotes angiogenesis, have been developed to limit tumor growth. Bevacizumab (Avastin), an anti-VEGF monoclonal antibody, is the first appr...
Source: Cancer and Metastasis Reviews - September 14, 2021 Category: Cancer & Oncology Source Type: research

Targeting KRAS in pancreatic cancer: new drugs on the horizon
AbstractKirsten Rat Sarcoma (KRAS) is a master oncogene involved in cellular proliferation and survival and is the most commonly mutated oncogene in all cancers. Activating KRAS mutations are present in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases and are implicated in tumor initiation and progression. Although KRAS is a critical oncogene, and therefore an important therapeutic target, its therapeutic inhibition has been very challenging, and only recently specific mutant KRAS inhibitors have been discovered. In this review, we discuss the activation of KRAS signaling and the role of mutant KRAS in PDAC develo...
Source: Cancer and Metastasis Reviews - September 9, 2021 Category: Cancer & Oncology Source Type: research