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”.

Olaparib shows improved survival in Phase 3 trial, FDA approval granted

"FDA Approves Olaparib for First-Line Maintenance of BRCA-Mutated, Advanced Ovarian Cancer

https://tinyurl.com/yayx3drb

On December 19, 2018, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor olaparib (Lynparza) for the maintenance treatment of adult patients with deleterious or suspected deleterious germ-line or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

The FDA also approved BRACA analysis CDx to be used by health-care professionals to identify patients with advanced ovarian cancer who have a germ-line BRCA mutation and are eligible for olaparib following response to platinum-based chemotherapy

Lynparza (olaparib), a poly ADP-ribose polymerase (PARP) inhibitor, co-developed by AstraZeneca and Merck (known as MSD outside the US and Canada), has succeeded in a phase 3 trial (SOLO-3) held in patients with relapsed BRCA-mutated (BRCAm) advanced ovarian cancer by meeting the primary endpoint.

https://tinyurl.com/y9fcbckz

SOLO-3 is the first Phase 3 trial for a PARP inhibitor to demonstrate a positive result versus chemotherapy in advanced ovarian cancer where effective options are needed".

(The third step in testing an experimental drug (or other treatment) in humans. Phase 3 trials are conducted to confirm and expand on safety and effectiveness results from Phase 1 and 2 trials, to compare the drug to standard therapies for the disease or condition being studied, and to evaluate the overall risks and benefits of the drug. This trial phase recruits a large group of people with the disease or condition, usually ranging from 1,000 to 3,000 participants. The Food and Drug Administration (FDA) reviews results from Phase 3 trials when considering a drug for approval.)

Does opportunistic salpingectomy save lives and money?

 

The cost-effectiveness of opportunistic salpingectomy versus standard tubal ligation at the time of cesarean delivery for ovarian cancer risk reduction

https://tinyurl.com/ybevpsa4

Opportunistic salpingectomy is a cost-effective strategy recommended for ovarian cancer risk reduction at the time of gynecologic surgery in women who have completed childbearing.

https://tinyurl.com/y79oseav

We aimed to evaluate the cost-effectiveness of opportunistic salpingectomy compared to standard tubal ligation (TL) during cesarean delivery.

In 10,000 women desiring sterilization with cesarean, opportunistic salpingectomy would result in 17 fewer ovarian cancer diagnoses, 13 fewer ovarian cancer deaths, and 25 fewer unintended pregnancies compared to TL.

In women undergoing cesarean with sterilization, opportunistic salpingectomy is likely cost-effective and may be cost saving in comparison to TL for ovarian cancer risk reduction.

Well, it’s Christmas!

 “Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis

https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0407-1

To the best of our knowledge, this is the first meta-analysis to summarize evidence between total dietary fiber intake and different types or sources of dietary fiber intake and risk of ovarian cancer. The risk of ovarian cancer was reduced by 22% in the group of highest dietary fiber intake compared with the lowest”

http://www.eatingwell.com/recipes/17938/holidays-occasions/christmas/

'We bring gifts of gold, myrrh, and ovarian cancer treatment'

https://lra.le.ac.uk/handle/2381/39946

Extracts from Boswellia sp. (Frankincense), used for centuries as herbal medicine in Asia, have known anti-inflammatory properties and anti-cancer potential alone or in combination with other chemotherapies. This suggests that frankincense may be useful for overcoming drug resistance, and it could also lead to an improved survival rate for patients with late-stage ovarian cancer”.

“A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373023/

As one year closes and another begins, I find myself reflecting on ovarian cancer diagnostics. It is truly humbling how little we have accomplished in this field over the last half-century. So let us awake on a future Christmas morning with newfound clarity. Let us transform how we categorize ovarian cancer, how we identify ovarian cancer, how we treat ovarian cancer, and possibly how we screen for cancer in general. It did not take long for the Nuclear Age to change our worldview or for the Information Age to profoundly alter our daily lives; with any luck, it will not take long to revisit our approach to early diagnostics for ovarian cancer. If Ebenezer Scrooge can change his ways…”