What's New and Yet to Come?

Promising New Drugs and Therapeutic Approaches for Treatment of Ovarian Cancer—Targeting the Hallmarks of Cancer 

https://tinyurl.com/bdzu8nr5 

As we begin a new year, it's an opportune time to examine both current advances in ovarian cancer treatment and potential breakthroughs on the horizon. 

Recent progress in ovarian cancer treatment has been marked by the advent of personalised medicine, which targets specific genetic and molecular variations in individual patients. This approach has led to improved survival rates through the introduction of novel therapeutics, particularly PARP and angiogenesis inhibitors. 

Innovative drug delivery mechanisms are revolutionizing treatment, most notably through antibody-drug conjugates (ADCs). The latest example is MIRV (mirvetuximab soravtansine), which has shown promise in treating recurrent ovarian cancer. 

This article examines ongoing phase III clinical trials and evaluates their potential impact on patient care. Immunotherapy, while previously showing limited efficacy, is experiencing a renaissance through combination approaches. The DUO trial, which combines PARP inhibition with checkpoint inhibition, suggests a promising new direction in treatment. 

This year's basic research emphasizes tumour-specific characteristics rather than broader patient parameters, aiming to identify novel targets for personalised therapy. These developments offer renewed hope for improving outcomes in ovarian cancer treatment.

BRCA, even more worrisome

New tool puts reproductive risk for BRCA carriers into perspective

https://tinyurl.com/24hrpkzp

Ever since the 1960s, the familial risk of breast and ovarian cancer has been recognised as the hereditary breast and ovarian cancer syndrome (HBOC). The genetic mutations responsible were shown to be located on chromosomes 17 and 13 and labelled BRCA1 and 2.

These mutations are dominant, meaning only one copy of the gene needs to be affected. More recently the effect of both genes bearing the mutation causing childhood disease and early onset cancers is becoming clearer. Many women carrying one of the BRCA mutations are unaware of this additional risk.

What this means is that if both a child’s mother and father carry a BRCA mutation, that child has a 75% risk of both genes being affected and a 100% risk of being a carrier.

The major risk to the child with dual BRCA mutation is a bone marrow disorder, Fanconi’s Anaemia. This is an incurable condition with a limited lifespan of about 30 years and much associated cancer.

Obviously, the risk of this happening is much greater in populations where there is a high BRCA mutation, such as Ashkenazi Jews and the Shetlanders. Advice about possible dual inheritance should form part of genetic counselling.

Your gut biome affects ovarian cancer immune response

Integrative multi-omics analysis uncovers tumour-immune-gut axis influencing immunotherapy outcomes in ovarian cancer

https://tinyurl.com/3h5wuk33

About 50% of all ovarian cancer has an increased T cell infiltration suggesting a strong immune response. This is associated with good survival.

Targeted immune therapy which inhibits checkpoint activity unfortunately thus far has not been shown to be effective against ovarian cancer. This study looked at the impact of the faecal microbiome on immune checkpoint blockade (ICB).

Using data from another study, which tested the effect of ICB for recurrent ovarian cancer, a subgroup of patients showed a significant benefit (30%). These patients had a different microbiome when compared to those patients who did not have much benefit.

This information suggests that manipulation of the gut biome could be an aid to survival for patients with recurrent ovarian cancer.

Why does alcohol cause OC?

Alcohol Consumption and Breast and Ovarian Cancer Development: Molecular Pathways and Mechanisms

https://tinyurl.com/39h72xhz

A link between alcohol consumption and increased risk of breast cancer is well known. It now is becoming clear that a similar association with ovarian cancer exists albeit less clear cut.

Alcohol abuse is common, it is estimated that alcohol is the cause of 5% of all deaths. The exact mechanism of increased cancer risk remains uncertain. Recent understanding suggests that in the case of ovarian cancer three important mechanisms are responsible. These are; hormonal modulation, DNA damage, and cellular oxidation.

Alcohol is metabolised in the liver, with acetaldehyde as an intermediate product. Both these substances can damage DNA and disrupt repair. The presence of alcohol in the body causes oxidative stress, with an imbalance of free radicals and antioxidants. In good health free radicals, which are oxygen containing molecules with an uneven electron charge, have an important function to control disease. If the balance is disrupted as with alcohol consumption cellular damage may occur.

Hormonal effects of alcohol are due to disruption of  the normal metabolism via aromatase, sometimes causing breast cancer and Low-Grade Ovarian Cancer.  More extensive damaging effect with increased ovarian cancer risk is suspected,

Further understanding will help to determine whether a safe level of alcohol consumption is possible and enable individuals to make their own risk assessment.

Which is best?

The prognostic influence of hospital type, method of first histological confirmation and time to chemotherapy in patients with advanced primary ovarian cancer

https://tinyurl.com/cburpu7d

There is a constant effort to improve the management of ovarian cancer. It is clear that the best chance of complete cure is at the time of the initial surgery. If the cancer can be completely cleared, survival is more likely.

Towards this end a proposed change in management has been developed, with a two-stage process, whereby an initial limited procedure is performed, to obtain a tissue biopsy, prior to complete clearance.

This review of 115 women with ovarian cancer, looks at whether there is any difference in outcome when the two-stage process is used. Also, the hospital type where the first procedure occurred may be significant, in that complete surgery at a centre of excellence has been shown to be advantageous for survival.

Results from the review showed no difference in overall survival, there was a delay in starting chemo for those having two-stage management. A surprising number of women, (10 out of 55 who had two-stage procedures), developed a metastasis at the entry port for the biopsy. Meaning that progression free survival was worse for them.

Is pollution causing OC?

Outdoor Air Pollution Exposure and Ovarian Cancer Incidence in a United States–Wide Prospective Cohort Study

https://tinyurl.com/yjzydbdz

Ever increasing rates of cancer in young patients has raised the concern that this is a consequence of pollution. For the first time evidence supporting this theory in relation to ovarian cancer is available.

Pollution presents mainly in two forms: particulate material such as micro plastics and sulphur, or gaseous such as nitrous dioxide and ozone. Using information from the” Sisters”study, which enrolled more than 50,000 women who had at least one sister with a history of breast cancer, it was possible to show how rates of ovarian cancer varied in relation to different geographic areas, with different pollution levels.

Results from this prospective analysis showed a positive association with increased nitrous dioxide levels but no association with particulate pollution or increased ozone. Nitrous dioxide is found in the atmosphere as the result of combustion mostly from fossil-fuelled transport or internal heating. Elimination of this pollutant would be a good side effect of more use of electric vehicles.

Is it cost-effective?

Cost and Clinical Implications of Utilizing Homologous Recombination Deficiency Status to Guide First-Line Maintenance Therapy Selection in Advanced Ovarian Cancer

https://tinyurl.com/yrydv7t8

With success comes overuse. A typical example of this is the widespread use of enzyme inhibitors, such as PARPi in ovarian cancer, for women who because of their genotype are unlikely to have any benefit.

The current cost in the US to treat 100 women with PARPi for ovarian cancer is just over  $US 62 million for the 5-year treatment course. This imposes a strain on personal and community finances. If these patients are screened using a biomarker guide (BMG), the cost overall is reduced, (by 17.5%), despite the significant cost  of performing BMG on 100 women.

Savings from treatment also include reduced clinical costs due to prolonged survival and better health. For costly treatment such as targeted enzyme inhibition, it is important to ensure it is only used when most cost-effective. This study shows that for each dollar spent on HRD testing, another twenty-six dollars of savings will result.