Taking a Full Snapshot of Cancer Biology: Deciphering the Tumor Microenvironment for Effective Cancer Therapy in the Oncology Clinic

Abstract Background Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established. Case presentation We described a case of Trousseau’s syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation–positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up. Conclusions This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy.

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Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms22020791 ◽

2021 ◽

Vol 22 (2) ◽

pp. 791

Author(s):

Qi Liu ◽

Bayonle Aminu ◽

Olivia Roscow ◽

Wei Zhang

Keyword(s):

Tumor Microenvironment ◽

Cancer Therapy ◽

Therapeutic Agents ◽

Biological Processes ◽

Post Translational Modification ◽

E3 Ligases ◽

Tumor Microenvironments ◽

Cellular Immune ◽

Ubiquitin Conjugating Enzymes ◽

Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

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