Metastatic melanoma treatment: Combining old and new therapies

Davey, Ryan J.; Westhuizen, André van der; Bowden, Nikola A.

doi:10.1016/j.critrevonc.2015.11.011

Cited by 69 publications

(59 citation statements)

References 165 publications

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“…Immunotherapy with either IFN-α or IL-2 or chemotherapy with dacarbazine is thus largely ineffective for patients with these cancers, and these therapies are also associated with serious adverse effects (42)(43)(44). In contrast, immunotherapy with ipilimumab (a mAb against CTLA-4) or nivolumab (a mAb against PD-1), both of which are thought to abrogate the inhibitory checkpoint for cytotoxic T cell activity, has recently been approved as a promising treatment for both advanced melanoma and renal cell carcinoma (42)(43)(44). Effective immunotherapy with Abs that target tumor-specific antigens on the cell surface of these carcinomas and thereby kill the cancer cells (by ADCC or ADCP) has yet to be developed.…”

Section: Discussionmentioning

confidence: 99%

Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy

Yanagita¹,

Murata²,

Tanaka³

et al. 2017

JCI Insight

126

153

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Section: Discussionmentioning

confidence: 99%

Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy

Yanagita¹,

Murata²,

Tanaka³

et al. 2017

JCI Insight

126

153

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“…The monofunctional alkylating agents dacarbazine (DTIC) and temozolomide (TMZ) are approved in USA and frequently used for the treatment of melanoma for first-line therapy, but for most patients DTIC and TMZ treatment fails [5], [6]. Due to the inherent drug-resistant characteristic of this disease, chemotherapy by TMZ is an ineffective mean of treating malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the inherent drug-resistant characteristic of this disease, chemotherapy by TMZ is an ineffective mean of treating malignant melanoma. The reasons for the chemoresistant phenotype in human melanoma are not well understood and are probably multifactorial [5].…”

Section: Introductionmentioning

confidence: 99%

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition

Tse

Chen

et al. 2017

Redox Biology

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Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKβ inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy.

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“…The clinical scenario drastically changed after the introduction of immune checkpoints inhibitors (ICI), a new class of targeted drugs able to activate the immune system against cancer cells, and showing efficacy for both solid tumours and haematological malignancies, with striking results leading to unexpected survival gains for advanced/unresectable melanoma [4]. Melanoma is actually the first cancer subtype where these immune-activating agents showed an advantage in survival over standard chemotherapy, and data from large clinical trials confirmed a substantial benefit with prolonged survival [5].…”

mentioning

confidence: 96%