Inpharma 1316 - 1 Dec 2001

Fragile histidine triad gene:potential cancer therapy?

Fragile histidine triad (FHIT) gene therapy maypotentially be useful in the treatment of early-stagecancer and in cancer prevention, report researchersfrom the US. They evaluated preclinical studiesassessing the use of the FHIT tumour suppressor gene incancer therapy and similar studies involving Fhit proteinexpression.

Marked reduction in Fhit expressionThe researchers identified 26 studies that analysed a

total of 1948 primary cancers and 9 studies thatanalysed a total of 408 precancerous lesions. Overall,60% of the primary cancers and 31% of theprecancerous lesions showed loss or marked reductionof Fhit protein expression. The researchers commentthat data from these studies suggest that we can use‘Fhit loss as an early detection marker and FHITalterations as targets for early gene therapy’.

In fact, reintroduction of the FHIT gene into 26 tumourderived cell lines from human lung, head and neck,oesophageal, gastric, cervical, pancreatic and kidneycancers led to inhibition of tumour cell growth in vitroand/or tumourigenicity in vivo in 17 of 30 cell lineexperiments.

Inhibition of tumour developmentData from animal studies also indicate that ‘loss of 1

FHIT allele in an organ or tissue contributes tomalignancy’. The researchers demonstrated thatcarcinogen-induced upper gastrointestinal tracttumours can be successfully inhibited by gene transferof the FHIT gene using viral vectors in heterozygous Fhit+/- knockout mice.

The researchers conclude that exogenous Fhitexpression appears to inhibit cancer cell growth ‘at leastin part through caspase-dependent apoptosis’, andsuggest that FHIT gene therapy can be used as apreventive treatment as well as a therapeuticintervention in carcinogen-related precancerous lesionsin tissues such as the oesophagus and lung.Ishii H, et al. Potential cancer therapy with the fragile histidine triad gene: reviewof the preclinical studies. JAMA: the Journal of the American Medical Association286: 2441-2449, 21 Nov 2001 800876730

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Inpharma 1 Dec 2001 No. 13161173-8324/10/1316-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved