Easy testing for defective DNA repair

Easy testing for defective DNA repair

Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial

https://tinyurl.com/dmncvndv

Defective DNA repair causes about half of all ovarian cancer. For those women who develop this cancer, and are shown to have the defect, treatment with PARP inhibitors (PARPi) will extend progress-free survival (PFS). Identifying these women is costly and unreliable. A new finding obtained from an otherwise inconclusive clinical trial may lead to a cheaper and dependable test.

The Solace 2 trial sought over a 4-year period to prove that stimulating an immune response before starting conventional therapy would improve PFS for women with advanced high grade serous ovarian cancer (HGSOC). It is well known that HGSOC depresses immunity, and this accounts for the usual bad outcomes. The trial did not achieve the key indicator, which was 36-week PFS for two-thirds of the treatment group.

An unexpected finding from the trial was the effectiveness of a blood test for defective DNA repair. This test identifies T cell checkpoints found with this defect, meaning it may soon be possible to quickly and easily determine who will benefit from PARPi therapy.

All about theranostics

Australian ovarian cancer breakthrough enters human trials

https://tinyurl.com/ye245f8f

Medicine is full of new words or neologisms. Mostly these are produced by PR agencies looking for a memorable brand name for a new drug. Sometimes the new name marks a dramatic shift in medical care. One such is theranostics a complex noun first used in 1997 to name a marriage of therapy and diagnosis.

Theranostics are combinations of antibodies and radiopharmaceuticals currently being used in the treatment of prostate cancer and carcinoid. The radiopharmaceutical of choice is lutetium-177 which is an isotope with a short half-life and an intense Beta emitter. Beta radiation is of high energy with low penetration and highly toxic, Standard systemic brachytherapy with Beta emitters is likely to kill the patient before killing the cancer.

The antibody combination targets the radiation to the cancer cell meaning only a low non-fatal dose is required. The antibody is produced to bind to a specific cancer cell antigen receptor. The theranostic is used to identify which cancers show this antigen by PET scan. Prostate cancer exhibits an antigen called PSMA. 

This study describes a new antigen found with ovarian cancer called CDCP1. A clinical trial is commencing looking at whether PET scan using a new theranostic combination is effective in identifying ovarian cancer cells which show this antigen receptor. Hopefully this will lead to more effective treatment.

Understanding Cachexia

Molecular subtypes of human skeletal muscle in cancer cachexia

https://tinyurl.com/3y3dun9v

Cachexia is a grave indicator of near death for women with ovarian cancer. It is defined as a weight loss of more than 10% or a BMI of less than 20 in patients with ovarian cancer.

Why some patients become cachexic has been a mystery, the weight loss is predominately due to decrease of muscle bulk with associated weakness and impaired mobility.

This prospective study involved next-generation genetic sequencing, using muscle biopsy tissue, obtained from 84 patients with cancer, at the time of their initial surgery. The whole muscle RNA signature (RNAome) showed two distinct subtypes. Only subtype I patients progressed to cachexia with an inflammatory reaction causing muscle wasting.

This breakthrough in understanding suggests it may be possible to predict cachexia and employ treatment to prevent it. Also, the difference in the RNAome between the two groups may suggest a metabolic pathway of disease.