Robert A. Casero, Jr.

Prof. Robert A. Casero, Jr.

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Research Focus & Metrics

Academic Career Length

38Years (1989-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 December 2004 in Cell
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Journal Article
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YSYujiang Shi
Yujiang Shi
FLFei Lan
Fei Lan
CMCaitlin Matson
Caitlin Matson
PMPeter Mulligan
Peter Mulligan
JWJohnathan R. Whetstine
Johnathan R. Whetstine
YSYang Shi
Yang Shi

4 September 2018 in Nature Reviews Cancer
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Journal Article
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RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
Tracy Murray StewartTracy Murray Stewart
Tracy Murray Stewart
APAnthony E. Pegg
Anthony E. Pegg
Advances in our understanding of the metabolism and molecular functions of polyamines and their alterations in cancer have led to resurgence in the interest of targeting polyamine metabolism as an anticancer strategy. Increasing knowledge of the interplay between polyamine metabolism and other cancer-driving pathways, including the PTEN–PI3K–mTOR complex 1 (mTORC1), WNT signalling and RAS pathways, suggests potential combination therapies that will have considerable clinical promise. Additionally, an expanding number of promising clinical trials with agents targeting polyamines for both therapy and prevention are ongoing. New insights into molecular mechanisms linking dysregulated polyamine catabolism and carcinogenesis suggest additional strategies that can be used for cancer prevention in at-risk individuals. In addition, polyamine blocking therapy, a strategy that combines the inhibition of polyamine biosynthesis with the simultaneous blockade of polyamine transport, can be more effective than therapies based on polyamine depletion alone and may involve an antitumour immune response. These findings open up new avenues of research into exploiting aberrant polyamine metabolism for anticancer therapy.

1 May 2007 in Nature Reviews Drug Discovery
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RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
LMLaurence J. Marton
Laurence J. Marton

11 March 2012 in Nature Medicine
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TSTino Schenk
Tino Schenk
WCWeihsu Claire Chen
Weihsu Claire Chen
SGStefanie Göllner
Stefanie Göllner
LHLouise Howell
Louise Howell
LJLiqing Jin
Liqing Jin
AZArthur Zelent
Arthur Zelent

29 August 2011 in Proceedings of the National Academy of Sciences
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AGAndrew C. Goodwin
Andrew C. Goodwin
CSChristina E. Destefano Shields
Christina E. Destefano Shields
SWShaoguang Wu
Shaoguang Wu
DHDavid L. Huso
David L. Huso
XWXinQun Wu
XinQun Wu
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
It is estimated that the etiology of 20–30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenicBacteroides fragilis(ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that purifiedB. fragilistoxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic epithelial cells, resulting in SMO-dependent generation of ROS and induction of γ-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6 mice is associated with increased SMO expression and treatment of mice with an inhibitor of polyamine catabolism,N1,N4-bis(2,3-butandienyl)-1,4-butanediamine (MDL 72527), significantly reduces ETBF-induced chronic inflammation and proliferation. Most importantly, in the multiple intestinal neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon tumorigenesis by 69% (P< 0.001). The results of these studies indicate that SMO is a source of bacteria-induced ROS directly associated with tumorigenesis and could serve as a unique target for chemoprevention.

15 September 1998 in Proceedings of the National Academy of Sciences
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HHHyo Chol Ha
Hyo Chol Ha
NSNilantha S. Sirisoma
Nilantha S. Sirisoma
PKPeriannan Kuppusamy
Periannan Kuppusamy
JZJay L. Zweier
Jay L. Zweier
Patrick M. WosterPatrick M. Woster
Patrick M. Woster
RJRobert A. Casero, Jr.
Robert A. Casero, Jr.
The polyamines are small organic cations that are absolutely required for eukaryotic cell growth. Although their growth requirements are well established, the molecular functions of the polyamines are ill-defined. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. The polyamine spermine, which is normally found in millimolar concentrations in the nucleus, is shown here to function directly as a free radical scavenger, and adducts formed as a result of this function are identified. These data suggest that spermine is a major natural intracellular compound capable of protecting DNA from free radical attack.