Predictive, preventive, personalized and participatory (P4) ovarian cancer medicine*

Precision targeted therapy of ovarian cancer

https://doi.org/10.1016/j.jconrel.2016.10.014

Previously scientists researched cancer with a reductionist approach, examining single targets or pathways. Years of research have made many improvements in the field of oncology, but it appears there is a limit to improving patient mortality from ovarian cancer.

Morphological and molecular studies show ovarian cancer is a collection of disease subtypes with diverse origins and significantly different clinical behaviors. Tumours are comprised of various differentiated cell types, which form a unique microenvironment. Treating all forms of ovarian cancer with a single “miracle” treatment appears impossible.

New approaches to cancer medicine are required in order to improve treatment outcomes. The concept of systems biology should be applied to ovarian cancer to develop predictive, preventive, personalized and participatory (P4) cancer medicine. *

Systems biology takes a broader, more holistic approach to understanding the basic biology of cancer, including genetics, signaling pathways, etc. and their interaction, which form the complex biological system found in a tumour.

Targeted therapeutics demonstrates a clinical promise in the future. The key is to discover and diagnose tumours as early and accurately as possible. This is the main obstacle for ovarian cancer care and needs to be improved in order to improve outcomes and reduce mortality rates.

* Medicine that focuses on the integrated diagnosis, treatment and prevention of disease in individual patients. Hood 2002

Will A.I. manage ovarian cancer?

Machine learning predicts individual cancer patient responses to therapeutic drugs with high accuracy

https://www.nature.com/articles/s41598-018-34753-5

'Precision or personalized cancer medicine is a clinical approach that strives to customize therapies based upon the genomic profiles of individual patient tumors.

The search for significant correlations in cancer-relevant datasets is a task ideally suited to computers and specifically to a branch of artificial intelligence called machine learning.*

A series of studies was designed to evaluate the accuracy of our model and to predict the responses of cancer patients, to chemotherapeutic drugs, from genomic profiles.

In addition to accurately predicting the response of cancer cell lines to 7 chemotherapeutic drugs, the model predicts the sensitivities of ovarian cancer patients to the same drugs. The accuracy of the model to predict responses to treatment, across 175 patients ranged from 81.5% to 82.6%".

* (“Machine learning can figure out how to perform important tasks by generalizing from examples”.) – University of Washington

Does low-dose aspirin therapy help protect against developing ovarian cancer?

Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies

https://jamanetwork.com/journals/jamaoncology/article-abstract/2704211

This cohort study using data from the Nurses’ Health Study and Nurses’ Health Study II observed a 23% lower risk of ovarian cancer among current low-dose aspirin users compared with nonusers.  Among the 205 498 women there were 1054 cases of incident epithelial ovarian cancer. 

http://www.cancer.ca/en/research-horizons/3/1/3/could-aspirin-prevent-cancer/

One common hypothesis about how Aspirin may prevent cancer is through its anti-inflammation activity. Chronic inflammation is known to increase the risk of certain types of cancer, including colorectal and ovarian cancers.

https://jamanetwork.com/journals/jamaoncology/article-abstract/2704207

In the United States, almost half of adults aged 45 to 75 years take aspirin on a regular basis. For those who take aspirin regularly, there is a widespread belief in aspirin’s anticancer potential; in a 2015 study, 18% of Americans who took aspirin regularly said they were doing so to prevent cancer.

https://www.ctg.queensu.ca/cctg_news/new-ovarian-cancer-study-explores-possibility-prevention-strategy-aspirin

This current clinical trial tests whether aspirin may prevent ovarian cancer in women with BRCA1 or BRCA2 gene mutations. The women in the study have already decided to have preventive protective surgery and the trial will assess whether a low or standard dose of Aspirin for six months before the surgery reduces the incidence of pre-cancerous tissue damage in the resected ovaries and fallopian tubes.

Editorial from NEJM raises concerns about SOLO-1 (Olaparib) trial

 NEJM Quick Take: Improving outcomes in ovarian cancer

“Progress in BRCA-Mutated Ovarian Cancer

https://tinyurl.com/yag2thl2

Nearly all the patients in the SOLO1 trial had a germ-line mutation in BRCA1 or BRCA2 (BRCA1/2), and the results may not be generalizable to patients with either somatic BRCA mutations or wild-type BRCA genes. Despite a request from the Journal, Myriad Genetics has declined to provide the actual identity and distribution of the genetic variants detected

There were very real toxic effects, primarily related to the myelo-suppression that so commonly occurs with cancer treatments, and less than 50% of the patients in the olaparib group completed the 2-year treatment plan.

Will the dramatic improvement in progression-free survival translate to an overall survival benefit or even an improved cure rate?

Could long-term use of agents that interfere with repair of double-stranded DNA breaks result in the development of the myelodysplastic syndrome and acute leukemia?

Additional studies will be needed to evaluate the effect of PARP inhibitors in other, less susceptible populations, including patients who have other defects in the repair of double-stranded DNA breaks, somatic (tumor) BRCA1 mutations, epigenetically silenced BRCA1/2 expression, or even intact BRCA1/2 function in the context of ovarian cancer”.