IAP antagonists Birinapant and AT-406 efficiently synergise with either TRAIL, BRAF, or BCL-2 inhibitors to sensitise BRAFV600E colorectal tumour cells to apoptosis

Périmenis, P.; Galaris, Apostolos; Voulgari, Alexandra; Prassa, Margarita; Pintzas, Alexander

doi:10.1186/s12885-016-2606-5

Cited by 29 publications

(18 citation statements)

References 42 publications

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“…Although melanoma cells are largely insensitive to these mimetic drugs when used as single agents, combinations with TRAIL or TRAIL receptor agonists appear as promising [106]. Thus, the IAP antagonists Birinapant and AT-406 could sensitize BRAFV600E colorectal tumor cells for TRAIL-induced apoptosis [107].…”

Section: Discussionmentioning

confidence: 99%

Countering TRAIL Resistance in Melanoma

Eberle

2019

Cancers

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Melanoma of the skin has become a prime example for demonstrating the success of targeted cancer therapy. Nevertheless, high mortality has remained, mainly related to tumor heterogeneity and inducible therapy resistance. But the development of new therapeutic strategies and combinations has raised hope of finally defeating this deadly disease. TNF-related apoptosis-inducing ligand (TRAIL) represents a promising antitumor strategy. The principal sensitivity of melanoma cells for TRAIL was demonstrated in previous studies; however, inducible resistance appeared as a major problem. To address this issue, combination strategies were tested, and survival pathway inhibitors were shown to sensitize melanoma cells for TRAIL-induced apoptosis. Finally, cell cycle inhibition was identified as a common principle of TRAIL sensitization in melanoma cells. Mitochondrial apoptosis pathways, pro- and antiapoptotic Bcl-2 proteins as well as the rheostat consisted of Smac (Second mitochondria-derived activator of caspase) and XIAP (X-linked inhibitor of apoptosis protein) appeared to be of particular importance. Furthermore, the role of reactive oxygen species (ROS) was recognized in this setting. Inducible TRAIL resistance in melanoma can be explained by (i) high levels of antiapoptotic Bcl-2 proteins, (ii) high levels of XIAP, and (iii) suppressed Bax activity. These hurdles have to be overcome to enable the use of TRAIL in melanoma therapy. Several strategies appear as particularly promising, including new TRAIL receptor agonists, Smac and BH3 mimetics, as well as selective kinase inhibitors.

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Section: Discussionmentioning

confidence: 99%

Countering TRAIL Resistance in Melanoma

Eberle

2019

Cancers

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“…Unfortunately, in many cases antitumor drugs are not effective and they often have deleterious side effects ( Iwamoto et al, 2014 ; Li and Caeyenberghs, 2018 ). Most cancer biologists agree that there is a need for new antineoplastic therapies or cotherapies, and proapoptotic strategies seem to be promising against neoplastic diseases ( Chesi et al, 2016 ; Perimenis et al, 2016 ; Rathore et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Promising Antineoplastic Actions of Melatonin

et al. 2018

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Melatonin is an endogenous indoleamine with an incredible variety of properties and activities. In recent years, an increasing number of studies have investigated this indoleamine’s interaction with cancerous cells. In particular, it seems that melatonin not only has the ability to improve the efficacy of many drugs used in chemotherapy but also has a direct inhibitory action on neoplastic cells. Many publications underlined the ability of melatonin to suppress the proliferation of various cancer cells or to modulate the expression of membrane receptors on these cells, thereby reducing tumor aggressiveness to metastasize. In addition, while melatonin has antiapoptotic actions in normal cells, in many cancer cells it has proapoptotic effects; these dichotomous actions have gained the interest of researchers. The increasing focus on melatonin in the field of oncology and the growing number of studies on this topic require a deep understanding of what we already know about the antineoplastic actions of melatonin. This information would be of value for potential use of melatonin against neoplastic diseases.

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“…Moreover, studies have reported the enhanced antitumor activity of chemotherapeutic agents by Smac mimetics in various malignant cells (36)(37)(38)(39)(40). Several Smac mimetics, including AT-406 (38)(39)(40)(41)(42)(43), are currently undergoing clinical trials for treatment of various cancers alone or in combination with anticancer drugs (38)(39)(40)(41)(42)(43)(44)(45)(46). Smac mimetics are reported to exhibit synergistic effect in combination with DOX and facilitate cIAP1 degradation (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%