Published paper review 2:
After noting some unusual results in cancer patient treatment, a team of Swiss researchers for The Stockholm Breast Cancer Group embarked upon a decades-long trial, and subsequently published a study on the “Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients”.
Many of the patients who suffered with breast cancer underwent hormone therapy with tamoxifen. Hope flared, there was a marked reduction in tumors, which would be altogether wonderful news for those suffering from the disease. However, 30% of these patients relapsed with adverse reactions to the tamoxifen treatment.
Looking at the numbers, 30% may seem minor compared to the success stories, but the health of these patients wasn’t something researchers could ignore. What was causing the relapse and how would this affect treatment? It turns out that the culprit was actually polymorphism affecting in both the SULT1A1 gene, and cytochrome P450 2D6 (CYP2D6). Usually, the enzymes CYP2D6 (member of cytochrome D40 system) found in the liver and SULTIA 1 or Sulfrotransferase 1A1 (oh the complicated names!) were seen to metabolize the tamoxifen, increasing its efficiency. However, with polymorphism, there is a change in the placement of the nucleotide in these structures, preventing successful treatment.
From the small sample size of 679 breast cancer patients, 226 were able to provide were fresh frozen tumor tissues for analysis. Scientists sequenced the patients’ DNA which they then examined through polymerase chain reactions along with restriction enzymes. Throughout the study, doses of tamoxifen were given at 40 mg daily, for 2 years with a 10.7 year follow up time for the patients. Talk about a long time just to get some results!
The results were in… and it turns out that patients with the CYP2D6*4 allele showed a lower chance of resistance to tamoxifen therapy and there was a lower chance of risk and resistance seen with those homozygous for (having the same pair alleles for) SULTIA*1.
Further investigation showed that 60% of patients who had a combination of the two had a much lower chance of relapse with tamoxifen. This study, and many like it, changed the face of cancer treatment and drug delivery. Researchers were able to conclude that enzymes can act through metabolism in order to help, or hinder the endocrine treatment in breast cancer patients. Essentially, it shows that drugs should be targeted not only to a patient’s age and gender, but also to their genetic makeup, in order to deliver more effective treatment and aid in recovery.
Contributors: India, Roi (editor)