Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Luu, Anita K.; Viloria-Petit, Alicia

doi:10.3390/ijms21207595

Cited by 8 publications

(6 citation statements)

References 206 publications

(230 reference statements)

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“…Notably, several studies highlight the contribution of the mTOR pathway in mechanisms of drug resistance [2,52,105,[109][110][111][112][116][117][118]120]. In these mechanisms, mTOR holds a dual role.…”

Section: Discussionmentioning

confidence: 99%

“…Dual inhibition of mTOR and Kelch-like ECH-associated protein 1 (KEAP1) could reduce resistance to both selective compounds [111]. mTOR signaling is upregulated in osteosarcoma [112]. Threedimensional osteosarcoma in vitro model shows increased resistance to chemotherapy and insulin growth factor-1 receptor (IGF-1R)/mTOR targeting [113].…”

Section: Mtor Targeting and Mechanotransduction Interplay In Anticanc...mentioning

confidence: 99%

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mTOR Signaling Components in Tumor Mechanobiology

Gargalionis

Papavassiliou

Basdra

et al. 2022

IJMS

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Mechanistic target of rapamycin (mTOR) is a central signaling hub that integrates networks of nutrient availability, cellular metabolism, and autophagy in eukaryotic cells. mTOR kinase, along with its upstream regulators and downstream substrates, is upregulated in most human malignancies. At the same time, mechanical forces from the tumor microenvironment and mechanotransduction promote cancer cells’ proliferation, motility, and invasion. mTOR signaling pathway has been recently found on the crossroads of mechanoresponsive-induced signaling cascades to regulate cell growth, invasion, and metastasis in cancer cells. In this review, we examine the emerging association of mTOR signaling components with certain protein tools of tumor mechanobiology. Thereby, we highlight novel mechanisms of mechanotransduction, which regulate tumor progression and invasion, as well as mechanisms related to the therapeutic efficacy of antitumor drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Mtor Targeting and Mechanotransduction Interplay In Anticanc...mentioning

confidence: 99%

mTOR Signaling Components in Tumor Mechanobiology

Gargalionis

Papavassiliou

Basdra

et al. 2022

IJMS

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“…In Table 1 we present several biomechanics-inspired treatment strategies reviewed in the recent literature analyses. 71–73 …”

Section: Osteosarcoma Treatment Strategies Inspired By Cancer Biomech...mentioning

confidence: 99%

“… Based on the recent review articles by Shoaib et al, Belayneh et al, Luu and Viloria-Petit. 71–73 IGF-1R, insulin growth factor-receptor; OS, osteosarcoma. …”

Section: Osteosarcoma Treatment Strategies Inspired By Cancer Biomech...mentioning

confidence: 99%

Biomechanical Aspects in Bone Tumor Engineering

Menshikh,

Banicevic,

Obradovic

et al. 2024

Tissue Engineering Part B: Reviews

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In the past decades, anticancer drug development brought the field of tumor engineering to a new level by the need of robust test systems. Simulating tumor microenvironment in vitro remains a challenge, and osteosarcoma—the most common primary bone cancer—is no exception. The growing evidence points to the inevitable connection between biomechanical stimuli and tumor chemosensitivity and aggressiveness, thus making this component of the microenvironment a mandatory requirement to the developed models. In this review, we addressed the question: is the “ in vivo – in vitro ” gap in osteosarcoma engineering bridged from the perspective of biomechanical stimuli? The most notable biomechanical cues in the tumor cell microenvironment are observed and compared in the contexts of in vivo conditions and engineered three-dimensional in vitro models. Impact statement The importance of biomechanical stimuli in three-dimensional in vitro models for drug testing is becoming more pronounced nowadays. This review might assist in understanding the key players of the biophysical environment of primary bone cancer and the current state of bone tumor engineering from this perspective.

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“…Anti‐YAP/TAZ therapies work by affecting their upstream receptors, inhibiting YAP/TAZ nuclear localization or disrupting their interaction with TEAD and BRD4 (Rothzerg et al, 2021 ). Some inhibitors targeting YAP/TAZ directly or indirectly in OS include verteporfin, agave extract, dasatinib , and pazopanib (Luu & Viloria‐Petit, 2020 ). Verteporfin is the only low MW inhibitor which binds directly to YAP/TAZ and decrease cell migration, FAK levels in OS and β1 integrin levels in MSCs (Husari et al, 2019 ).…”

Section: Potential Mechanistic Therapies For Os Targeting Mechanobiologymentioning

confidence: 99%

Osteosarcoma mechanobiology and therapeutic targets

Shoaib

Fan

Irudayaraj

2021

British J Pharmacology

100

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Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is highly predisposed in Paget's disease of the bone, and both have common characteristic skeletal features due to rapid bone remodelling. Osteosarcoma prognosis is location dependent, which further emphasizes the likely contribution of the bone microenvironment in its pathogenesis. Mechanobiology describes the processes involved when mechanical cues from the changing physical microenvironment of the bone are transduced to biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies have been used to curb tumour progression by direct alteration of the physical microenvironment or inhibition of metastasis-associated mechanosensitive proteins. This review emphasizes the contribution of mechanobiology to the progression of osteosarcoma and sheds light on current mechanobiology-based therapies and potential new targets for improving disease management. Additionally, the many different 3D models currently used to study osteosarcoma mechanobiology are summarized.

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Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Cited by 8 publications

References 206 publications

mTOR Signaling Components in Tumor Mechanobiology

mTOR Signaling Components in Tumor Mechanobiology

Biomechanical Aspects in Bone Tumor Engineering

Osteosarcoma mechanobiology and therapeutic targets

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