Aspirin may hold the key for new
cervical cancer drugs
Helen Theron, UCT
The humble aspirin could hold new promise for the treatment of uterine
cervical cancer, a deadly cancer affecting 60 in every 100 000 South African
women. It has been reported that South Africa has the highest incidence of
cervical cancer in the world.
Cancer of the cervix is the most common cancer in
black (31.2 %) and coloured (22.9 %) South African women, second most common
cancer in Asian (8.9 %) and fourth most common cancer in white South African
women (2.7 %), the latter figure representing the disease's prevalence in the
developed world.
"It is a disease that needs to be caught early, but there are no
national screening programmes," says researcher Associate Professor Arieh
Katz, a Senior Wellcome Fellow in the Division of Medical Biochemistry at the
University of Cape Town (UCT). A Pap smear (named after Dr George Papanicolaou),
remains the best means of detecting the presence of pre-malignant lesions on the
cervix. By the time a woman shows symptoms; bleeding, secretions or abdominal
pain, it is usually too late to cure.
The disease is linked to socio-economic conditions and is particularly common
in less developed countries. Extensive laboratory and epidemiological evidence
has established that the human papillomavirus (HPV) is a major cause for the
development of cervical cancer. "In addition to HPV, women presenting with
cervical carcinoma show a high incidence of venereally transmitted disease,
genital warts, genital herpes and trichomonas infection," Katz notes.
Since 1999 Katz has been collaborating with Dr Henry Jabbour, who is a Senior
Scientist at the British MRC's Human Reproductive Sciences Unit at the
University of Edinburgh; to examine the role of two important enzymes, COX-1 and
COX-2 (cyclooxygenase) and their prostaglandin products in the development and
progression of cervical cancer, with a parallel effort to discover suitable drug
targets.
Essentially, the COX enzymes enhance the progress of cancer tumours by
supporting cell division, the growth of blood vessels in the tumour and by
reducing the rate of cell death.
The research team, which included PhD student Kurt Sales (who graduated in
June this year), found that cervical cancer tissue has elevated levels of both
COX-1 and 2 enzymes and their synthesized prostaglandin products. These
findings implicate COX enzymes in the growth of cervical tumours and suggest
that inhibitors to COX enzymes may provide effective treatment for cervical
cancer. The researchers' current task is to decipher the molecular mechanism by
which elevated COX enzymes influence the development and progression of cervical
cancers.
"Further research will examine the effects of prostaglandin on cervical
carcinomas and the specific biochemical signalling pathways and target genes
that allow the cells to become malignant," explains Jabbour. "In turn,
these findings will highlight possible intervention therapies that may suppress
or inhibit tumour growth or suppression."
Hope appears in the form of aspirin, already widely used in the treatment of
heart disease. According to Katz, a recent study of nurses in Britain had
revealed that nurses who routinely used aspirin had a lower incidence of colon
cancer. The tissue of the colon and the cervix is the same. The same active
ingredient in aspirin that acts as an anti-coagulant, or thins the blood, also
inhibits the COX enzymes that enhance the growth of colon and cervical cancers.
"But we need to understand more about COX enzymes to be sure that
aspirin will be beneficial, or at least slow the progress of cervical
cancer," Jabbour says.
The collaboration also involves PhD student Melissa Muller, one of two UCT
students to receive a highly prestigious Commonwealth Fellowship, awarded by the
British Council recently.
The one-year fellowship will allow Muller to work in Jabbour's laboratory for
two six-month periods beginning in January next year. "It is important for
this collaboration that she goes back and forward between the two institutions
to create an exchange of ideas," Jabbour adds.
Muller's work examines the effect of prostaglandin on the levels of COX
enzymes, which, in turn, promote tumorous cell growth. This is significant
research as semen contains large amounts of prostaglandin and can thus promote
cervical tumorigenesis in sexually active women.
(The collaboration involves Groote Schuur Hospital - through Dr Rob Soeters,
head of gynaecological oncology in the Department of Obstetrics and Gynaecology
and the Division of Anatomical Pathology at UCT).
For further details contact Professor Katz at (021) 406-6268 or katz@curie.uct.ac.za
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