Misunderstanding Ovarian Cancer - Dr Mark Burgin
09/12/21. Dr. Mark Burgin BM BCh (oxon) MRCGP discusses how a growing understanding is starting to challenge the political and medical decisions around this often fatal disease.
The Cancer Research UK website contains a detailed account of the 6th most common cancer in women (7,500/year women diagnosed in the UK).
Research in cancer is making some types such as breast cancer if not curable a chronic disease that can be managed long term.
Ovarian cancer is the most lethal of the gynaecological cancers because the majority are detected at late (stage III or IV) and it spreads in the peritoneal cavity.
Increasingly we are recognising that cancers in different parts of the body may have more in common than was thought.
Ovarian cancer does not start in the ovary
This extraordinary finding that ovarian cancer is serous (epithelial) rather than germ cell or stromal has been known for a while.
Recent findings of pre-malignant changes (STIC lesions) in the epithelial cells of fallopian tubes suggests that the fallopian tubes may be unusually susceptible.
Whilst it is not possible yet to reach these cells to test for early changes it is known that when the cells are shed they can travel into the uterus and out through the cervix.
TP53 gene mutations (carcinogen type) are found in the STIC lesions and the cancers and can be detected in the liquid-based type of cervical smear.
Why are normal fallopian tubessusceptible?
Most TP53 cancers occur in tissues which are exposed to carcinogens such as the gastrointestinal tract and the associated organs such as liver and pancreas.
Other tissues such as those exposed to urine and the lungs will come into contact with carcinogens but top of the list is ovary which should not be exposed (cervix by contrast is very low).
The explanation may come from expression of another marker WT1 in normal fallopian tubes which interacts with TP53 so that fallopian tubes susceptible.
As normal fallopian tubes already express WT1 even low levels of environmental carcinogens pooling in the pelvis would cause the changes.
A cure is near?
90% of ovarian cancer is the same type (serous epithelial) and the pattern of markers is similar in all examples of this type of cancer.
This suggests that there might be a single cause for most ovarian cancers which has implications on both prevention and treatment.
If the cause of ovarian cancer is that normal fallopian tube expresses WT1 then any treatment that targets that gene will be exceptionally useful in ovarian cancer.
PARP inhibitors have been developed to block a DNA repair mechanism important for tumour survival but also improves WT1 function.
Conclusions
Clinical practice often lags behind our understanding of disease from the misnaming of ovarian cancer to the failure to include tests for TP53 in cervical smears.
New drugs such as PARP inhibitors are being rationed for patients with ovarian cancer until they relapse despite the promising trials and otherwise poor prognosis.
Drug companies must repeat clinical trials for each new type of cancer slowing access to effective treatment which patients reading off label results self-fund.
Little work is being funded to find which environmental toxins are responsible for the TP53 gene mutations in ovarian cancer protecting industry from being sued.
Doctor Mark Burgin, BM BCh (oxon) MRCGP is on the General Practitioner Specialist Register and audits medical expert reports.
Dr. Burgin can be contacted This email address is being protected from spambots. You need JavaScript enabled to view it. and 0845 331 3304 website drmarkburgin.co.uk
1. Cancer Research UK website https://www.cancerresearchuk.org/
2. Arildsen Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method Sci Rep. 2019; 9: 15506.
3. Olivier M TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use Cold Spring Harb Perspect Biol. 2010 Jan;2(1)
Image ©iStockphoto.com/utah778
