Fragile histidine triad gene: potential cancer therapy?
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Inpharma 1316 - 1 Dec 2001 Fragile histidine triad gene: potential cancer therapy? Fragile histidine triad (FHIT) gene therapy may potentially be useful in the treatment of early-stage cancer and in cancer prevention, report researchers from the US. They evaluated preclinical studies assessing the use of the FHIT tumour suppressor gene in cancer therapy and similar studies involving Fhit protein expression. Marked reduction in Fhit expression The researchers identified 26 studies that analysed a total of 1948 primary cancers and 9 studies that analysed a total of 408 precancerous lesions. Overall, 60% of the primary cancers and 31% of the precancerous lesions showed loss or marked reduction of Fhit protein expression. The researchers comment that data from these studies suggest that we can use ‘Fhit loss as an early detection marker and FHIT alterations as targets for early gene therapy’. In fact, reintroduction of the FHIT gene into 26 tumour derived cell lines from human lung, head and neck, oesophageal, gastric, cervical, pancreatic and kidney cancers led to inhibition of tumour cell growth in vitro and/or tumourigenicity in vivo in 17 of 30 cell line experiments. Inhibition of tumour development Data from animal studies also indicate that ‘loss of 1 FHIT allele in an organ or tissue contributes to malignancy’. The researchers demonstrated that carcinogen-induced upper gastrointestinal tract tumours can be successfully inhibited by gene transfer of the FHIT gene using viral vectors in heterozygous Fhit +/- knockout mice. The researchers conclude that exogenous Fhit expression appears to inhibit cancer cell growth ‘at least in part through caspase-dependent apoptosis’, and suggest that FHIT gene therapy can be used as a preventive treatment as well as a therapeutic intervention in carcinogen-related precancerous lesions in tissues such as the oesophagus and lung. Ishii H, et al. Potential cancer therapy with the fragile histidine triad gene: review of the preclinical studies. JAMA: the Journal of the American Medical Association 286: 2441-2449, 21 Nov 2001 800876730 1 Inpharma 1 Dec 2001 No. 1316 1173-8324/10/1316-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Transcript of Fragile histidine triad gene: potential cancer therapy?
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
