Tumor Growth Accelerated By Stress Hormones
Chronic stress has recently been implicated as a factor that may accelerate the growth of tumors. However, the mechanisms underlying this effect have not been determined. But now, Anil Sood and colleagues, at the University of Texas MD Anderson Cancer Center, Houston, have generated data using human ovarian cancer cell lines and tumor specimens that indicate that stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in patients with ovarian cancer. They therefore suggest that targeting stress hormones and the signaling pathways that they activate might be of benefit to individuals with cancer.
Anoikis is the process by which cells are triggered to die when separated from their surrounding matrix and neighboring cells. Tumor cells that spread to other sites somehow escape anoikis. In the study, exposure of human ovarian cancer cells lines to either of the stress hormones norepinephrine or epinephrine protected them from anoikis. Similarly, in a mouse model of ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth. This effect was associated with activation of the protein FAK. The clinical significance of these data was highlighted by the observation that in human ovarian cancer patients, behavioral states related to greater stress hormone activity were associated with higher levels of activated FAK, which was in turn linked to substantially accelerated mortality.
Title: Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis
Source:
Karen Honey
Journal of Clinical Investigation
Drug Benefits Patients With Inherited Ovarian Cancer
A new type of cancer drug has shown promising results in patients with ovarian cancer linked to an inherited mutation, a disease for which current treatment options are limited. The trial results are published today in the Journal of Clinical Oncology.
Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, working with pharmaceutical company KuDOS Pharmaceuticals, now a subsidiary of AstraZeneca *, found the experimental drug olaparib shrank or stabilised tumours in around half of ovarian cancer patients bearing BRCA1 or BRCA2 mutations.
The five-year survival rate for ovarian cancer is just 40 per cent as the majority of patients are diagnosed with an advanced form of the disease. Most patients initially respond well to radical surgery and platinum and taxane-based chemotherapy, but relapse after an average of 18 months. Subsequent treatments generally become less effective as patients build up resistance.
“There is an urgent need to find new drugs for women diagnosed with ovarian cancer,” says Professor Stan Kaye, Head of the Section of Medicine at the ICR and Head of the Drug Development Unit at The Royal Marsden Hospital and a Cancer Research UK-funded scientist. “Olaparib is still in early-stage testing but the results so far are very encouraging. These findings raise the possibility that carefully selected patients in future may well be offered olaparib as an alternative to chemotherapy during the course of their treatment.”
Between 2005 and 2008, about 50 women with confirmed or suspected BRCA1 or BRCA2 mutations began treatment with olaparib in a dose escalation and single-stage expansion of a Phase I trial. Twenty patients responded with their tumours shrinking or with significant falls in their ovarian cancer marker CA125, or both. The disease also stabilised in a further three patients. The drug was effective for an average of seven months, while several patients are still taking olaparib for nearly two years. Side-effects were generally mild, especially when compared to current chemotherapy treatments. Read more