Clinical and Molecular Responses in Lung Cancer Patients Receiving Romidepsin

Schrump, David S.; Fischette, Maria R.; Nguyen, Dao M.; Zhao, Ming; Li, X.; Kunst, Tricia F.; Hancox, Ana; Hong, Julie A.; Chen, G.A.; Kruchin, E.; Wright, John J.; Rosing, Douglas R.; Sparreboom, Alex; Figg, William D.; Steinberg, Seth M.

doi:10.1016/s1525-7304(11)70818-x

Cited by 89 publications

(25 citation statements)

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“…Several thousands of ECGs and hundreds of LVEF evaluations were conducted in lymphomas and lung patients. [63][64][65] Post treatment T-wave flattening or ST segment depression and QTc intervals lengthening were observed in the majority of patients, as well as sporadic findings including sinus tachycardia, mild hypotension and premature atrial or ventricular complexes. However these abnormalities were not associated with elevation of cardiac enzyme (troponin I or CPK-MB) or with altered left ventricular function, even in a cohort of 16 patients treated for six months and regardless of prior anthracycline exposure, and none required pharmacologic intervention.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

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A work in progress: The clinical development of histone deacetylase inhibitor

Marsoni¹,

Damia²,

Camboni³

2008

Epigenetics

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It has been widely recognized that histone deacetylases (HDAC) are promising targets in the field of oncology. An impressive body of preclinical research points to the ability of HDAC inhibitors (HDACIs) to modulate a wide variety of cellular functions, including cell differentiation, cell cycle progression, apoptosis, cytoskeletal modifications and angiogenesis. Originally developed as epigenetic drugs because of their ability to inhibit histones deacetylation, HDACIs are now being considered also because of their effects on other acetylation-regulated proteins with pivotal roles in transformed cells. This review will highlight the clinical development of HDACIs in oncology and will try to discuss the several major open clinical issues challenging the successful clinical development of HDACIs, with a particular emphasis on the spectrum of activity of these agents, the best development strategy in solid tumors, the cardiac side effects and bio-markers to be used in clinical trials.

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Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

“…67 On the contrary, the ongoing phase II studies of depsipeptide in solid tumors are demonstrating marginal single agent activity of the drug in colorectal, renal, hormone resistant prostate and lung cancer. 65 …”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

A work in progress: The clinical development of histone deacetylase inhibitor

Marsoni¹,

Damia²,

Camboni³

2008

Epigenetics

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show abstract

“…I). (64) did not obtain significant results using romidepsin. In the study by Vansteenkiste et al (65), the endpoint was not reached due to adverse events, which were predominantly caused by a high dose of vorinostat.…”

Section: Preclinical Studies Of Hdacis In Nsclcmentioning

confidence: 80%

HDAC Inhibitors: A New Radiosensitizer for Non-small-cell Lung Cancer

Zhu

et al. 2015

Tumori

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For many decades, lung cancer has been the most common cancer and the leading cause of cancer death worldwide. More than 50% of non-small-cell lung cancer patients receive radiotherapy (alone or in combination with chemotherapy or surgery) during their treatment. The intrinsic radiosensitivity of tumors and dose-limiting toxicity restrict the curative potential of radiotherapy. Histone deacetylase inhibitors (HDACis) are an emerging class of agents that target histone deacetylase and represent promising radiosensitizers that affect various biological processes, such as cell growth, apoptosis, DNA repair, and terminal differentiation. Histone deacetylase inhibitors have been found to suppress many important DNA damage responses by downregulating proteins in the homologous recombination and nonhomologous end joining repair pathways in vitro. In this review, we describe the rationale for using HDACis as radiosensitizers and the clinical evidence regarding the use of HDACis for the treatment of non-small-cell lung cancer.

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“…Bacterial products can also combat cancer through inhibition of the HDAC enzyme. Romidepsin (FK228), a naturally occurring depsipeptide isolated from Chromobacterium violaceum, is a potent HDAC inhibitor with anticancer activity against leukemia, colon cancer and neuroblastoma cell lines, human tumor xenografts and murine tumors, and is therefore expected to be a novel and promising anticancer drug, currently under clinical evaluation in the USA (Ueda et al, 1994;Schrump et al, 2008;Piekarz et al, 2009;Mizutani et al, 2010;Panicker et al, 2010). The mechanism of FK228 induction of cancer demise is incompletely known but it seems associated with the ability of this compound to induce hydrogen peroxide synthesis, activation of caspases and programmed cell death (Mizutani et al, 2010).…”

Section: The Microbial World Of Anticancer Drugsmentioning

confidence: 99%