Epithelial mesenchymal transition

The Mechanism and Dynamic Regulation of Epithelial to Mesenchymal Transition in Ovarian Cancer

http://tinyurl.com/5rajk8zw

Understanding of ovarian cancer has increased, with the recognition of epithelial mesenchymal transition, (EMT), which develops in about 50%. EMT results in loss of adhesion with disruption of the normal tissue structure. Metastasis is inevitable with EMT, the cancer is more aggressive, and survival is worse. 

This review of the available literature describes the process which leads to EMT together with information about the significance and possible treatment.

EMT occurs because of epigenetic change to the chromosome of the cancer cell, it does not involve genetic mutation. Epigenetic change may involve cross linking and folding of cancer cell DNA and is potentially reversible.

EMT is a response to the environment, it may be due to low oxygen or glucose levels, mechanical stress or chemo effects. Previously it was thought to be a binary “all or nothing” change but now is described as partial with various degrees of penetration. It seems that partial EMT is more lethal. Understanding of EMT will lead to better-targeted personalised care.

Hysterectomy not grounds for divorce

Hysterectomy not grounds for divorce

http://tinyurl.com/4hmhwfwe

When considering the impact of ovarian cancer on relationships and family it is wise to remember the ethnic context. This recent case in the Madras High Court will have caused concern but it is illustrative of some pressures that women face after surgery that are not often discussed.

The Appeal Court in Madras supported the findings of a lower court which stated that removal of a uterus as part of initial treatment for ovarian cancer did not constitute mental cruelty to the husband and dismissed the appeal. 

The husband’s case was that the denial of the ability to have children was cruel to him and that the cancer had been present before the marriage and concealed. Divorce was sought by the husband under the Hindu Marriage Act which unlike in most western countries does not have a “no fault” separation clause, meaning that cause needs to be shown. This has changed recently.

Although outrageous to some, this action should be recognised for its context. Inheritance is very significant in the Indian culture which is collectivist in nature; meaning that individuals expect their relatives to be their guardian especially in old age. This was partially supported by the court which said that the wife should not unreasonably obstruct surrogacy or adoption.

More hope for platinum resistance

FDA Grants Fast Track Status to Rinatabart Sesutecan for FRα-Expressing Ovarian Cancer

http://tinyurl.com/2t5t8pv4

In November 2022 the FDA granted accelerated approval of a new drug; Elahere which improves survival for patients who have platinum resistant ovarian cancer. This was the first approval of an antibody/drug conjugate (ADC).

Now, a second fast track development by the FDA of a similar drug; Rina-S shows the importance of this treatment for those women. Both antibodies act by attaching to a cell membrane protein, folate receptor 𝛼, (FR𝛼), enabling intracellular access for the cytotoxic drugs, which destabilise cancer cell DNA, causing cell death. 

FR𝛼 is found in about 60% of ovarian cancer, Elahere has been shown to be effective in the MIRASOL trial when there is high expression of FR𝛼 (75% of all cancer cells).

FDA approval in this way is a vote of confidence that finally there is an alternative treatment for those women unlucky enough to be platinum resistant. Further information from clinical trials currently underway will more clearly show the role and potential benefits of ADC therapy.

Common drugs with unexpected effects

Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins

http://tinyurl.com/y8ut3nn5

Some commonly used drugs; metformin for type II diabetes and statins which alter cholesterol metabolism have been shown to increase survival from ovarian cancer. Understanding of why this is so has emerged which may support the inclusion of low cost readily available treatment alternatives for ovarian cancer.

Free fluid in the peritoneal cavity known as ascites is frequently part of advanced ovarian cancer, ascites alters the insulin and cholesterol pathways through metabolic reprogramming. This change in metabolism results in immune suppression and promotes tumour growth.

It is now thought that adding metformin and statins to standard therapy will increase response to chemotherapy, prevent T cell exhaustion, and enhance immunotherapy