Chemoprevention in patients with genetic risk of colorectal cancers

Laukaitis, Christina M.; Erdman, Steven H.; Gerner, Eugene W.

doi:10.2217/crc.12.22

Cited by 8 publications

(4 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical work with DFMO has supported this concept, although it has still to reach general acceptance for cancer therapy. Notable encouraging results include positive effects on anaplastic gliomas 81 , ongoing clinical trials on neuroblastoma 82,83 and prevention of colorectal cancer 84,85 . In spite of a recent review that erroneously indicated that clinical trials of DFMO have been abandoned because of its toxicity 86 , the safety and therapeutic value of DFMO is well established.…”

Section: Targeting Of Polyamine Metabolismmentioning

confidence: 99%

Polyamine metabolism and cancer: treatments, challenges and opportunities

2018

View full text Add to dashboard Cite

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.

show abstract

Section: Targeting Of Polyamine Metabolismmentioning

confidence: 99%

Polyamine metabolism and cancer: treatments, challenges and opportunities

2018

View full text Add to dashboard Cite

show abstract

“…Aspirin and piroxicam in combination with DFMO have been tested in animal studies and showed promising results [ 74 , 75 ]. A phase II clinical trial with aspirin and DFMO combination therapy to test for adenoma recurrence is underway [ 76 ]. The NSAIDs sulindac and celecoxib have been tested in animals and in clinical trials in combination with DFMO with encouraging outcomes [ 28 , 29 , 30 , 31 , 61 , 62 , 68 , 70 , 77 , 78 ].…”

Section: Colon Cancermentioning

confidence: 99%

Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases

LoGiudice

Abuan

et al. 2018

Medical Sciences

View full text Add to dashboard Cite

The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC is potentially a drug target for any disease state where rapid growth is a key process leading to pathology. The compound was originally discovered as an anticancer drug, but its effectiveness was disappointing. However, DFMO was successfully developed to treat African sleeping sickness and is currently one of few clinically used drugs to combat this neglected tropical disease. The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa. In recent years, renewed interest in DFMO for hyperproliferative diseases has led to increased research and promising preclinical and clinical trials. This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma.

show abstract

“…DFMO is clinically approved for the treatment of infection with a specific species of trypanosome, the parasite responsible for African sleeping sickness (15). DFMO is extremely well tolerated and is actively being studied in clinical trials as a chemopreventive agent in gastrointestinal and other cancers (16,17) and in combination with other agents in the treatment of neuroblastoma and other malignancies (18)(19)(20). The idea of targeting ODC expression and activity at multiple steps, from transcription to stability to activity, is attractive, because the development of resistance to all mechanisms occurring at once is unlikely.…”

Section: Identifying An Effective Drug Targeting Ahr To Reduce Polyammentioning

confidence: 99%

Targeting the aryl hydrocarbon receptor/polyamine biosynthesis axis of evil for cancer therapy

Casero¹

2018

Journal of Clinical Investigation

View full text Add to dashboard Cite

The polyamine metabolic pathway has been considered a rational target for antineoplastic therapy since it was discovered that polyamines are absolute requirements for tumor initiation, growth, and, in some instances, survival. Although several promising preclinical studies have demonstrated the critical nature of polyamines for tumor growth, the clinical success of agents targeting polyamine metabolism have been lacking. In the accompanying article, Bianchi-Smiraglia et al. identify both a new target and new drug that inhibits polyamine biosynthesis, reduces intracellular polyamines, and inhibits the growth of several models of human multiple myeloma. These results are both intriguing and provide promise for moving such a strategy to the clinic.

show abstract

Chemoprevention in patients with genetic risk of colorectal cancers

Cited by 8 publications

References 93 publications

Polyamine metabolism and cancer: treatments, challenges and opportunities

Polyamine metabolism and cancer: treatments, challenges and opportunities

Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases

Targeting the aryl hydrocarbon receptor/polyamine biosynthesis axis of evil for cancer therapy

Contact Info

Product

Resources

About