More about PARP

Revealing the selective mechanisms of inhibitors to PARP-1 and PARP-2 via multiple computational methods

https://tinyurl.com/ycskk646

         One of the most exciting developments in the treatment of ovarian cancer in recent times has been the use of new drugs called PARP inhibitors. These drugs act to prevent the repair of DNA chromosome material in the nucleus of cancer cells.       

         Certain groups of women have genetic predisposition to have an over-expression of PARP enzymes in their metabolism, this is most often inherited but may be acquired. Initially it was thought only women with the BRCA1/2 mutation were affected but now it seems up to about 45% of women who have ovarian cancer may benefit from PARP inhibition.

         Of course in cell metabolism nothing is simple and further study has described 17 variants of PARP enzymes. There are side effects of PARP inhibition, one of the most significant being damage to the bone marrow which can result in leukaemia. The PARP2 variant seems the problem, as inhibition of this makes the marrow effect more probable.

         This review describes new therapy in development, which selectively causes PARP1 inhibition, which is the effective suppression therapy for ovarian cancer but does not affect PARP2. This customised treatment of ovarian cancer would be a great benefit.

Baby powder withdrawn from sale

Johnson & Johnson Consumer Health Announces Discontinuation of Talc-based Johnson’s Baby Powder in U.S. and Canada

https://tinyurl.com/ya84otz3

         The link between ovarian cancer and use of talc on the perineum is controversial. There have been many court actions against Johnson and Johnson as manufacturers of talc alleging liability. Large imposition of punitive damages has been awarded and appeals launched.

         This week Johnson and Johnson have announced that the manufacture and sale of talc-based baby powder will be discontinued in the US and Canada

         In the announcement Johnson and Johnson deny any liability for cancer or other disease but state that because of the adverse publicity, sales of baby powder have been significantly reduced. They also state that during the Covid-19 pandemic other more important products have priority

No benefit for participants in clinical trials

Are cancer patients better off if they participate in clinical trials? A mixed methods study

https://tinyurl.com/yalas5uo

         There is an overemphasis on the value of clinical trials, especially by the media, which seek to sensationalise preliminary reports of therapy that subsequently is shown to be no improvement on current practice. Less than 5% of all phase I clinical trials result in any change to treatment.

         It is also incorrect that participation in clinical trials results in better outcomes for patients with cancer and those patients who do enter clinical trials have better care. This study looked at the attitudes of treating physicians and nurses regarding the value of clinical trials and also at outcomes for participants.

         The results were that most treating medical staff are convinced that clinical trials provide better care than standard therapy and that together with the psychological benefits of greater patient involvement in their disease, improved outcomes. 

         A review of available reports over the last ten years, which reported outcomes on members of trials versus non-members, showed no benefit in terms of improved outcomes.  The psychological benefit is called “Trial Effect”, the review showed no evidence of any advantage

Neoadjuvant therapy may be deleterious

Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer

https://tinyurl.com/y7aj9zna

         It is well established for stage III/IV ovarian cancers that the more complete the removal at initial surgery the better the outcome. It is known that chemotherapy prior to the procedure, known as neoadjuvant therapy, improves the surgical result due to reduction in size of the cancer.

         This study looked at about 500 patients, one third of whom had neoadjuvant chemotherapy, the others having surgery on presentation. Treatment-free interval times and platinum resistance were compared in both groups.

         There was no difference in platinum resistance, (which indicates the sensitivity of the cancer to chemotherapy), in either group. Patients who had chemotherapy prior to surgery had significantly shorter treatment free intervals suggesting earlier recurrence of disease. 

         No explanation is given; it is possible that the group treated with neoadjuvant therapy may have been less well at the time of initial presentation.

Serum CA 125 and early cancer

The generally low sensitivity of CA 125 for FIGO stage I ovarian cancer diagnosis increases for endometrioid histotype.

https://tinyurl.com/yd2d7yk5

         The value of an abnormal serum CA125 test in the diagnosis of early ovarian cancer remains undetermined. In this series the level of serum CA125 was measured for patients with early cancer and also those with borderline ovarian tumours.

         The sensitivity of an abnormal CA125 level with stage I ovarian cancer was low at 54%, meaning 46% were falsely negative. However, the likelihood of an abnormal serum CA125 level with benign ovarian tumour is low at 1.29 suggesting only three per hundred benign tumours will have abnormal serology.

         Stage I endometrioid ovarian cancers; most commonly found in endometriosis patients, have a greater sensitivity with only 28% false negative serum CA125 serology.