Pulling the plug on BCL-XL

Jeng, Paul S; Cheng, Emily H.

doi:10.1038/nchembio.1256

Cited by 10 publications

(8 citation statements)

References 10 publications

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“…Although we could not identify any predictor of RR to chemotherapy among the selected biomarkers, our results demonstrated that high expressed Bcl-2 was associated with shorter OS in patients with advanced EPNEC. This finding could be further explored and if more evidence emerges, Bcl-2 could be a potential new therapeutic target in G3 NEC, although anti-Bcl-2 therapies have not been successfully developed so far [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer

Rego

Medeiros

Braghiroli

et al. 2017

ecancer

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BackgroundSmall cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities.Materials and MethodsThis is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1.ResultsFrom July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02).ConclusionEPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.

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Section: Discussionmentioning

confidence: 99%

Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer

Rego

Medeiros

Braghiroli

et al. 2017

ecancer

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“…In addition, it has been shown that most cancers depend on more than one antiapoptotic Bcl-2 member for survival. The discovery of new selective inhibitors of antiapoptotic proteins is thus important for the search for anticancer drugs [ 84 , 85 , 86 , 87 ].…”

Section: Biological Activitiesmentioning

confidence: 99%

Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae)

et al. 2015

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Plants of the Lauraceae family are widely used in traditional medicine and are sources of various classes of secondary metabolites. Two genera of this family, Beilschmiedia and Endiandra, have been the subject of numerous investigations over the past decades because of their application in traditional medicine. They are the only source of bioactive endiandric acid derivatives. Noteworthy is that their biosynthesis contains two consecutive non-enzymatic electrocyclic reactions. Several interesting biological activities for this specific class of secondary metabolites and other constituents of the two genera have been reported, including antimicrobial, enzymes inhibitory and cytotoxic properties. This review compiles information on the structures of the compounds described between January 1960 and March 2015, their biological activities and information on endiandric acid biosynthesis, with 104 references being cited.

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“…Nevertheless, for those used in clinical trials, resistance due to overexpression of the non-targeted proteins (mainly Mcl-1) was identified suggesting that efficient treatment may require simultaneous inhibition of multiple anti-apoptotic Bcl-2 proteins. 11 Natural products or derivatives of natural products represent 75% of the 175 drugs used in cancer chemotherapy. 12 In 2008, we conducted a biological screening on Malaysian plant extracts, leading to the isolation of a new sesquiterpene dimer that we named meiogynin A 1.…”

Section: Bioorganic and Medicinal Chemistry Lettersmentioning

confidence: 99%

Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1

Desrat

Pujals

Colas

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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The biological evaluation of a natural sesquiterpene dimer meiogynin A 1, is described as well as that of five non-natural analogues. Although active on a micromolar range on the inhibition of Bcl-xL/Bak and Mcl-1/Bid interaction, meiogynin A 1 is not cytotoxic on three cell lines that overexpress Bcl-xL and Mcl-1. Contrarily, one of its analogues 6 with an inverted configuration on the side chain and an aromatic moiety replacing the cyclohexane ring was active on both target proteins, cytotoxic on a micromolar range and was found to induce apoptosis through a classical pathway.

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Pulling the plug on BCL-XL

Cited by 10 publications

References 10 publications

Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer

Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer

Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae)

Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1

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