• Publications
  • Influence
Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor.
A direct comparison between 6-acrylamido-4-anilinoquinazoline and an equally potent but reversible analog shows that the irreversible inhibitor has far superior in vivo antitumor activity in a human epidermoid carcinoma xenograft model with no overt toxicity at therapeutically active doses.
Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality
A screen identifies a drug that specifically kills glycolysis-dependent cancer cells by inhibiting glucose uptake and identifies a class of compounds, the 3-series, exemplified by STF-31, which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells onGLUT1 for survival.
A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation.
A quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, andDNMT3B as well as competing with S-adenosylmethionine in the methylation reaction and provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy.
A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types
Results show that inhibition of p110α alone has the potential to block growth factor signalling and reduce growth in a subset of tumours.
Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling.
Evidence that p110beta and p110delta can play a role in insulin signalling is provided and the first evidence that there can be functional redundancy between p110 isoforms is provided.
Mechanism of Action and Preclinical Antitumor Activity of the Novel Hypoxia-Activated DNA Cross-Linking Agent PR-104
PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy.
Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)
  • W. Denny
  • Medicine, Biology
    Journal of biomedicine & biotechnology
  • 19 March 2003
It is expected that continued studies to optimize the bystander effects and other properties of prodrugs and the activated species they generate will contribute to improvements in the effectiveness of suicide gene therapy.
Tumor-activated Prodrugs—A New Approach to Cancer Therapy
  • W. Denny
  • Biology, Medicine
    Cancer investigation
  • 1 January 2004
A wide variety of chemistries have been explored for the selective activation of TAP, including the reduction of quinones, N-oxides, and nitroaromatics by endogenous enzymes or radiation; the cleavage of amides by endogenous peptidases; and hydrolytic metabolism by a variety of exogenous enzymes, including phosphatases, kinases, amidases, and glycosidases.
Gemcitabine sensitization by checkpoint kinase 1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells
The data suggest the inhibition of this Chk1-mediated Rad51 response to gem citabine-induced replication stress is an important factor in determining gemcitabine chemosensitization by Chk 1 inhibition in pancreatic cancer cells.
An experimental and mathematical model for the extravascular transport of a DNA intercalator in tumours.
The utility of the MM model for determining extravascular transport parameters is demonstrated, and it is indicated that much of the impediment to diffusion of basic DNA intercalators in tumour tissue may arise from lysosomal sequestration rather than DNA binding.