- Generic heart medication shown to prolong ovarian cancer patients’ survival

Even despite prognostic factors and co-morbidities associated with poorer outcomes

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MD Anderson News Release 08/23/2015

In a first-of-its-kind study, researchers demonstrate a benefit in overall survival among epithelial ovarian cancer (EOC) patients receiving generic heart medications known as beta-blockers.  Survival was shown to be greatest among those prescribed first-generation nonselective beta-blockers. According to The University of Texas MD Anderson Cancer Center investigators, the drugs block the effects of stress pathways involved in tumor growth and spread.  With further research, they may also prove beneficial in conjunction with other treatment regimens and across other cancer types.

Published today in the journal CANCER, the findings are the result of a multi-institutional retrospective analysis of the medical records of 1,425 women with ovarian cancer treated between 2000 and 2010. Researchers compared overall survival among patients with documented beta-blocker use during chemotherapy and those without. Among the 269 patients who received beta-blockers, 193 (71.7 percent) received beta-1-adrenergic receptor selective agents (SBBs) and the remaining patients received nonselective beta antagonists (NSBBs). The research team found:

• For patients receiving any beta-blocker, the median overall survival was 47.8 months versus 42 months for nonusers.
• Median overall survival based on beta-blocker receptor selectivity was 94.9 months for those receiving NSBBs versus 38 months for those receiving SBBs.
• Even among patients with hypertension, a longer median overall survival was observed among users of NSBBs compared with nonusers (90 months versus 38.2 months).

This study builds on a large body of research by principal investigator Anil Sood, M.D., professor in Gynecologic Medical Oncology and Cancer Biology at MD Anderson. It showed that stress hormones fuel progression of ovarian and other cancers, and that beta-blockers – among the most proven drugs in cardiovascular medicine – might be a new way to stifle that effect. 

Anil Sood, M.D.

“Beta-blockers treat a variety of conditions, such as heart disease, high-blood pressure, glaucoma and migraines. They target a receptor protein in heart muscle that causes the heart to beat harder and faster when activated by stress hormones,” Sood said. “Our research has shown that the same stress mechanisms impact ovarian cancer progression, so these drugs could play a new role in cancer treatment.”

According to Sood, the usefulness of beta-blockers was unclear until now. “The ability to show improved survival using nonselective agents – which inhibit a specific stress pathway – is the culmination of years of research into ovarian cancer biology and pathogenesis.”

He added that beta-blocker users in the study presented at a higher stage of disease, had an increased average BMI and were more likely to be hypertensive. All these factors were associated with decreased survival, yet those who received beta-blockers had either equivalent or improved overall survival. Further examination revealed that NSBB users had improved overall survival regardless of the presence of such prognostic factors or comorbidities. This was not true for patients who took SBBs.

Although further study is needed, these results highlight the importance of adrenergic receptor-β2 (ADRB2), a signaling pathway important to ovarian carcinogenesis and targeted by NSBBs (versus the ADRB1 pathway targeted by SBBs).

Ovarian cancer is the 5th most deadly cancer among women, accounting for more deaths than any other female reproductive system cancer.  An estimated 21,290 new cases are diagnosed, and some 14,180 women die from the disease each year in the U.S., according to the American Cancer Society.  

Future trials will seek to identify patients who would benefit most from beta-blocker use and the best beta-blocker for a specific tumor type based on adrenergic receptor expression. Then they potentially could be used as an adjuvant therapy during surgical recovery and chemotherapy to decrease tumor growth, delays in wound healing and metastasis. Beta-blockers may also reduce cancer-related psychological distress in newly diagnosed patients, according to the study authors.

There are currently two clinical trials, one led by MD Anderson, evaluating the combination of chemotherapy and propranolol (a type of NSBB) on cancer biology and on stress modulators in patients with newly diagnosed EOC. According to Sood, the preliminary data from these feasibility trials will be used to design prospective, randomized clinical trials examining NSBBs on patient outcomes.  

“The stratification of patients by beta-blocker use and selectivity in this study makes it unique among all other studies examining the impact of these drugs on cancer. It also builds on the mounting evidence that beta-blockers may become a key treatment component for many patients in the future,” said Sood.

Portions of this study were supported by National Institutes of Health grants (CA140933, CA104825, CA109298, P50CA083639, U54CA151688, U54CA96300, U54CA96297, and CA016672), an Ovarian Cancer Research Fund program Project Development Grant, the Department of Defense (grants OC073399, W81XWJ-10-0158, and OC100237), the Betty Ann Asche Murray Distinguished Professorship, the RGK Foundation, the Gilder Foundation, the Blanton-Davis Ovarian Cancer Research Program, and a Gynecologic Cancer Foundation-St. Louis Ovarian Cancer Awareness grant. One of the researchers has acted as a paid consultant for Incyte Pharmaceuticals and received research funding from Egen Pharmaceuticals.

Other researchers contributing to this study include: Robert L. Coleman, M.D., Alpa M. Nick, M.D., Pedro T. Ramirez, M.D., Lois M. Ramondetta, M.D., Diana Urbauer, Jack L. Watkins, all from MD Anderson; Susan K. Lutgendorf, Ph.D. from University of Iowa; Sanjeev Kumar, M.B., B.S. from the Mayo Clinic; Koji Matsuo, M.D., from Mercy Medical Center; Kathryn Squires, M.D. and Premal H. Thaker, M.D., M.S. from Washington University School of Medicine.

Bron:  http://www.mdanderson.org/newsroom/news-releases/2015/beta-blocker-ovarian-cancer.html

- Stand van zaken: tweede recidief bevestigd

8 juli 2015

Mijn tweede recidief is 'officieel' bevestigd door de CT-scan waarop 3 nieuwe uitzaaiingen in de buiklymfeklieren te zien zijn. Inoperabel.
Aanleiding voor de scan was de uitkomst in juni van de verhoogde CA125 waarde (10). Omdat de CA125 voor mij een hele betrouwbare indicator is gebleken, betekent elke stijging ook daadwerkelijk tumorvorming.
Hoewel de oncoloog in eerste instantie zei "niks aan de hand", stond ik erop een CT-scan te laten maken gezien eerdere ervaringen.

Op 7 juli met internist-oncoloog dr. J.M.L. Stouthard haar lange termijn visie op mijn behandelplan doorgesproken en besloten de chemo een paar maanden uit te stellen en te starten met de hormoontherapie Tamoxifen (hoewel slechts 10% kans op aanslaan).
Deze behandeling schijnt minder belastend te zijn en bestaat uit pillen.
Wordt vervolgd.

- Nieuwsbericht: Protein in Ovarian Cancers Deactivates Immune System Response

July 06, 2015 | Ovarian Cancer, Gynecologic Cancers

By Leah Lawrence

Data from a new study has shown that ovarian cancer progression may be driven by the activation of an endoplasmic reticulum (ER) stress response factor called XBP1, which disrupts the function of dendritic cells and, subsequently, antitumor fighting T cells.

XBP1 is part of the ER stress response pathway—also called the unfolded protein response—that can allow tumors to grow and survive when they are deprived of nutrients and oxygen.

“Our findings suggest a strategy whereby a lethal cancer exploits the most conserved arm of the ER stress response in tumor-resident dendritic cells to disrupt their homeostasis, alter their local antigen-presenting capacity, and ultimately evade T cell-mediated immune control,” wrote study author Juan R. Cubillos-Ruiz, an instructor of immunology in medicine at Weill Cornell Medical College, and colleagues in the journal Cell.

“While the ER stress response, and especially XBP1 activation, was previously shown to promote tumorigenesis, we now propose that this integrated cellular pathway further supports malignant progression by inhibiting the development of protective antitumor immunity via manipulation of normal dendritic cell function,” they wrote.

To make this discovery, Cubillos-Ruiz and colleagues examined the tumor microenvironment and found that ovarian cancer promoted the modification of proteins located in the ER, which, in turn, induced XBP1 activation and produced a buildup of lipid molecules within dendritic cells.

The researchers then tested whether or not XBP1 could be targeted. They injected mice with aggressive primary and metastatic ovarian cancer with nanoparticles, microscopic polymers that carried a genetic molecule that can silence the XPB1 gene. Dendritic cells detect the nanoparticles as invaders, and ingest them. Once inside, the nanoparticles delivered the molecule that turns XBP1 off, allowing dendritic cells to tell the immune system to attack the cancer.

“Activating T cell immunity to eliminate tumor cells is the most promising anticancer strategy since the development of chemotherapy, as demonstrated by the shrinkage of melanoma in response to checkpoint blockers,” the researchers wrote. “However, in most cases, the optimal cytotoxic activity of such tumor-reactive T cells is drastically reduced precisely because cancer-associated dendritic cells are unable to support T cell function.”

The results of this analysis show that deletion of XBP1 can transform tumor dendritic cells into ovarian cancer infiltrating T cells. If further developed, targeting XBP1 using nanotechnology-based system may help to slow or prevent the recurrence of ovarian cancers, the researchers wrote.

- See more at: http://www.cancernetwork.com/ovarian-cancer/protein-ovarian-cancers-deactivates-immune-system-response#sthash.uYzLs7gb.dpuf

- 4 jaar geleden...

25 maart 2015

In verband met de aangifte inkomstenbelasting moest ik duiken in de medische situatie van 2014, heel confronterend.
En realiseerde mij ook opeens: precies vier jaar geleden had ik mijn eerste operatie... Een eeuwigheid geleden. Nog weet ik niet waar ik aan toe ben en hoe ik er aan toe ben. De afspraak van 6 maart met de gynaecoloog-oncoloog heb ik zelf afgezegd; 11 juni krijg ik de uitslag van mijn bloedonderzoek. Afschuwelijk spannend want voel weer van alles. Maar mijn lijf kan geen chemo aan momenteel en mijn geest nog minder.

- Leven in zalige onwetendheid

12 februari 2015

Goh, lang niet geschreven zie ik. En dat terwijl er zoveel is gebeurd en gebeurt...
Vandaag zelfs 15 pageviews, bijzonder! Ik vraag me altijd af wie de bezoekers zijn.
Maar om kort te gaan: met mij gaat het. Dat wil zeggen, ik leef in onwetendheid en geniet zoveel mogelijk van het leven. Heb het reizen, mijn grootste passie, weer opgepakt en daar heel ik pas echt van.
De bijeenkomsten bij de Bruno Groning Vriendenkring werken ook ondersteunend aan mijn streven zo veel mogelijk niet-patient te willen zijn.
Al blijf ik stiekem natuurlijk zo goed mogelijk op de hoogte van nieuwe ontwikkelingen etc.
Laatst was ik op een lotgenotenbijeenkomst in een inloophuis en de angst en stress sloegen onmiddellijk toe. Daarom blijf ik nog even op mijn wolkje zitten totdat ik het gevoel heb dat mijn lichaam en geest weer een chemokuur of operatie kunnen verdragen... dus tumorvorming of niet, voorlopig liever op reis in plaats van controles en behandelingen!