Putting cancer to sleep

Scientists Discover How To Reactivate Cancer’s Dormant “Kill Switch”

https://tinyurl.com/yeytv4es

Ovarian cancer presents late. The peak incidence is at age 75 which is about 10 years later than most cancers.  Theories about why this is so suggested that there is a period of dormancy, and that the cancer becomes overt because of some unexplained change.

This research suggests that many aggressive and hard to treat cancers including ovarian cancer hijack normal protective functions that would otherwise limit cancer invasion. This protective mechanism limits cellular metabolism by blocking DNA and RNA transcription,with consequent reduction in enzyme and protein activity which would otherwise promote cancer growth.

When this process is hijacked, the protection is lost. This research suggests that the protective mechanism can be restored using synthetic RNA fragments to alter cellular metabolism.

This discovery has the potential to provide a new target for precision therapy by restoring cancer dormancy.

We’ve been looking in the wrong place

Aged and BRCA mutated stromal cells drive epithelial cell transformation

https://tinyurl.com/mxs7nz32

Ovarian cancer is different, the commonest type called serous cancer presents late with metastasis. It has been known for some time that the most likely site of origin for this cancer is the fallopian tube as a precursor abnormality of the epithelium occurs known as a serous tubal intraepithelial cancer (STIC) lesion.

These lesions have a high risk of conversion to invasive cancer with subsequent spread to ovary, meaning that ovarian cancer is always advanced at the time of presentation.

It seemed logical that STIC lesions would develop in the epithelium as a result of conversion from adaptable stem cells. This research from the US suggests that the initial change occurs in cells from the sub-epithelial layer known as the stroma. The responsible cells are called mesenchymal stem cells (MSC). Usually, these cells assist in repair of tubal tissues. Women with known increased risk of ovarian cancer such as those with the BRCA mutation have increased numbers of MSC, which are present before ovarian cancer develops.

Further understanding of the role of the fallopian tube in the cause of ovarian cancer supports the role of preventative surgery for high-risk women.

Alarming weight loss

Adipose tissue loss during neoadjuvant chemotherapy: a key prognostic factor in advanced epithelial ovarian cancer

https://tinyurl.com/55ykwrm4

Early understanding of probable poor survival may be useful in planning the management of ovarian cancer. This study looks at changes in body composition that occur after chemo prior to surgery (neoadjuvant chemo).

This prospective study looked at 53 patients with advanced ovarian cancer who received three cycles of chemo before surgery. Using CT scans before and after chemo the muscle and fat volumes were measured. All patients showed loss of muscle and fat. This was greater for those women who were obese before treatment.

Loss of muscle volume did not alter survival. Loss of fat however was a marker of poor survival especially when the fat loss was visceral within the abdomen rather than subcutaneous. This was even more marked when the weight loss was rapid. The authors suggest that nutritional support to avoid weight loss may be beneficial for ovarian cancer patients undergoing neoadjuvant chemo.

A catchy title

Leader cells promote immunosuppression to drive ovarian cancer progression in vivo

https://tinyurl.com/myym6w6v

In medical research having a catchy name for any recent findings is a good tool to promote visibility and attract funding. A recent article from the Hudson Institute demonstrates this.

Ovarian cancer presents late with metastasis having already occurred for 75% of cases at the time of diagnosis. This study looks at a feature of aggressive ovarian cancer, whereby cells at the margins of the cancer known as “Leader cells”, develop invasive outgrowths formed of keratin-14, a protein similar to skin and hair proteins.

The presence of these leader cells promotes invasion of surrounding tissues, the exact nature of why this occurs is unclear but studies in mice ovarian cancer cells show immune suppression. As a result, the normal protective immune reaction to invasion, mediated by T cell lymphocytes is inactivated.

Caution about the significance of these results is expressed by the authors who suggest this study is limited and further investigation is warranted. Despite this caution the term “Leader cells” seems to have caught the attention of the popular press.

Robots are the future

Feasibility of Robotic Surgical Approach in Peritoneal Carcinomatosis

https://tinyurl.com/4h24fnfr

Complete clearance of ovarian cancer at the time of the first surgery remains the most important factor in a cure. Sometimes with advanced cancer the distant spread to the lining of the abdomen, (peritoneal carcinomatosis), makes clearance difficult if not impossible.

New surgical techniques using robotic assistance are becoming commonplace for some surgical procedures, notably prostate cancer. Robotic surgery is safer with less morbidity and mortality, there is better visualisation of small structures and is more likely to achieve complete clearance.

This retrospective study of 16 patients, 9 of whom had ovarian surgery, showed that robotic surgery is feasible and safe. Because of the cost and due to limited resources, randomised prospective clinical trials, looking for better outcomes will be required before this technique becomes more readily available.

Indicators of survival

The impact of preoperative immuno-nutritional status on prognosis in ovarian cancer: a multi-centre real-world study

https://tinyurl.com/yeyspm3c

Two relatively simple indices of health may be obtained prior to surgery for ovarian cancer. These are the Prognostic nutritional Index (PNI) which is measured using the serum albumen and the Systemic Immune-inflammation Index (SII) calculated as a ratio of platelets to white cells in circulating blood.

This prospective survey looked at survival after surgery for women with ovarian cancer and the correlation to pre-operative health.

Results obtained from the study showed that those women with good nutritional health (high PNI) had better progress free survival and overall survival. Women whose immune status was good before surgery (high SII) had good progress free survival but slightly worse overall survival.

For those women whose nutritional and immune status were not good there was more platinum resistance and poor outcomes. Use of these markers gives important prognostic information and may alter management.

Vigil, partial FDA approval

The US FDA grants RMAT Designation to Gradalis’ Vigil for Advanced Ovarian Cancer

https://tinyurl.com/46bdjj7v

For women with ovarian cancer who don’t respond to maintenance therapy using PARP inhibitors there is new hope. The FDA has enabled fast access through the Regenerative Medicine Advanced Therapy, (RMAT) designation to a targeted treatment called Vigil, which is intended for use in patients who do not have defective DNA repair.

RMAT designation is used to speed the approval process of drugs which have shown encouraging impact on otherwise untreatable illness. Vigil is a new form of immunotherapy whereby cells from the patient’s own cancer are infected with a bacterial DNA fragment (a plasmid), and then injected back in to the donor, to promote an immune reaction similar to a vaccine.

Although this drug is only in a phase II clinical trial, early responses have shown promising improvements in progress free and overall survival.

The clinical trial titled VITAL is not recruiting currently and there are no Australian candidates. Following the FDA approval, phase III trials are expected soon.