Infectious Knockdown of CREB and HIF-1 for the Treatment of Metastatic Uveal Melanoma

Voropaev, Hanna; Vatkin, Maria Gimmelshein; Shneor, Dudi; Luski, Shahar; Honigman, Alik; Frenkel, Shahar

doi:10.3390/cancers11081056

Cited by 16 publications

(12 citation statements)

References 27 publications

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“…The resistance of hypoxic cells to RT and chemotherapy is a major problem in the treatment of cancer [30,31]. Malignant melanoma is also considered radioresistant, and research is ongoing to improve the efficacy of therapy in hypoxia [32,33]. The PpIX property that enhances • OH generation, which does not depend on the amount of dissolved oxygen, has the potential to improve RT effects of radioresistant tumors.…”

Section: Discussionmentioning

confidence: 99%

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

Hasegawa

Takahashi

Nagasawa

et al. 2020

IJMS

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Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3′-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

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Section: Discussionmentioning

confidence: 99%

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

Hasegawa

Takahashi

Nagasawa

et al. 2020

IJMS

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“…In agreement with these results, the ability of hexokinase 2, the initial and rate-limiting step in glycolysis, to regulate UM growth through the Warburg effect has been described [ 312 ]. The relevance of this study is represented by the use of vectors preferentially infecting proliferation cells, such as tumor ones, and by the possibility to use these vectors in combination with chemotherapy with the advantage of eventually reducing chemotherapy concentration and side effects [ 313 ].…”

Section: Uveal Melanomamentioning

confidence: 99%

Hypoxia-dependent drivers of melanoma progression

D’Aguanno

Mallone

Marenco

et al. 2021

J Exp Clin Cancer Res

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Hypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.

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“…Brouwer et al report on the association of the hypoxia-inducible factor 1 subunit alpha (HIF1α) and the von Hippel-Lindau protein (VHL) with BAP1 expression, inflammation, and tumor ischemia [36]. Consistent with this observation, Voropaev et al show that knockdown of the hypoxia mediators cAMP response element-binding protein (CREB) or HIF1α in UM cells by means of replication-competent retroviral vectors dramatically decreases UM tumor progression [32]. Brouwer et al also address tumor angiogenesis and show that the monosomy 3 and the loss of BAP1 is associated with an increased microvascular density [37].…”

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confidence: 91%