From Biology to Diagnosis and Treatment: The Ariadne’s Thread in Cancer of Unknown Primary

Mathew, Beatrice Gadiel; Aliyuda, Fine; Taiwo, Denis; Adekeye, Kehinde Adesola; Agada, Godwin; Sanchez, Elisabet; Ghose, Aruni; Rassy, Elie El; Boussios, Stergios

doi:10.3390/ijms24065588

Cited by 7 publications

(4 citation statements)

References 83 publications

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“…Epithelial–mesenchymal transition (EMT) refers to the transformation of epithelial cells into mesenchymal cells and is characterized by the loss of polarity. EMT plays a crucial role in tumor invasion and distant metastasis [ 112 ]. This process involves the disruption of cell adhesion junctions and alterations in gene expression, ultimately leading to enhanced invasive capabilities and metastatic potential of tumor cells [ 113 ].…”

Section: The Contribution Of Exosomes To Rccmentioning

confidence: 99%

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer

Boussios,

Devo,

Goodall

et al. 2023

IJMS

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Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

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Section: The Contribution Of Exosomes To Rccmentioning

confidence: 99%

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer

Boussios,

Devo,

Goodall

et al. 2023

IJMS

Self Cite

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“…Enhanced glycolysis is so common in neoplasia that it formed a basis for the approach to detect both primary and secondary tumors in the body by PET/CT. 18F-Fluorodeoxyglucose (FDG) is a glucose analog that is transported via glucose transporters into the cancer cells followed by hexokinase 2 (HK2)-mediated phosphorylation [24][25][26]. Thus, the areas of malignant growth are detected based on the increase in glucose uptake and utilization.…”

Section: Increased Glycolysis ("Warburg Effect")mentioning

confidence: 99%

Phytochemicals Target Multiple Metabolic Pathways in Cancer

Shuvalov,

Kirdeeva,

Daks

et al. 2023

Antioxidants

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Cancer metabolic reprogramming is a complex process that provides malignant cells with selective advantages to grow and propagate in the hostile environment created by the immune surveillance of the human organism. This process underpins cancer proliferation, invasion, antioxidant defense, and resistance to anticancer immunity and therapeutics. Perhaps not surprisingly, metabolic rewiring is considered to be one of the “Hallmarks of cancer”. Notably, this process often comprises various complementary and overlapping pathways. Today, it is well known that highly selective inhibition of only one of the pathways in a tumor cell often leads to a limited response and, subsequently, to the emergence of resistance. Therefore, to increase the overall effectiveness of antitumor drugs, it is advisable to use multitarget agents that can simultaneously suppress several key processes in the tumor cell. This review is focused on a group of plant-derived natural compounds that simultaneously target different pathways of cancer-associated metabolism, including aerobic glycolysis, respiration, glutaminolysis, one-carbon metabolism, de novo lipogenesis, and β-oxidation of fatty acids. We discuss only those compounds that display inhibitory activity against several metabolic pathways as well as a number of important signaling pathways in cancer. Information about their pharmacokinetics in animals and humans is also presented. Taken together, a number of known plant-derived compounds may target multiple metabolic and signaling pathways in various malignancies, something that bears great potential for the further improvement of antineoplastic therapy.

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“…The biological events leading to the undetermined primary site of metastatic cancer remain a mystery. Chromosomal abnormalities, gene expression, microvascular density, and immune microenvironmental changes in CUP have not been found to be specific 3 . Clinical studies on CUP have focused on the development of molecular diagnostics to facilitate accurate prediction of the primary site as well as specific treatments, rather than investigating current chemotherapy agents.…”

mentioning

confidence: 95%