Aug 152010
 

(Ovarian Cancer Parp Inhibitors Research) The experimental cancer drug olaparib, a drug in the promising class of drugs known as PARP Inhibitors,  produced promising results in patients with ovarian cancer linked to an inherited BRCA1 or BRCA2 gene mutation. The trial results were published in the Journal of Clinical Oncology on April 19th, 2010.

Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, working with pharmaceutical company KuDOS Pharmaceuticals, a subsidiary of AstraZeneca, found that olaparib shrank or stabilized tumors in approximately half of ovarian cancer patients possessing 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. “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 tumors shrinking or with significant falls in their ovarian cancer marker CA125, or both. The disease also stabilized in three patients. The drug was effective for an average of seven months. Notably, several patients are still taking olaparib (for nearly two years). Drug side-effects were generally mild, especially when compared to current chemotherapy treatments.

Platinum-based chemotherapy, particularly carboplatin, is one of the main treatments used for ovarian cancer. When this treatment ceases to be effective, theoretically, olaparib might be less effective too, so the ICR scientists examined whether olaparib would still benefit patients whose response to previous platinum-based drugs was limited. Finding new drugs to treat these “platinum-resistant” ovarian cancer patients (those who relapsed within six months of previous platinum therapy) is a particularly high priority as they have a lower chance of benefiting from re-treatment with chemotherapy and a poorer prognosis.

The research team found that the clinical benefit rate with olaparib was indeed higher — 70% — among patients with “platinum-sensitive disease” (disease recurrence more than six months after previous platinum therapy). Crucially, however, the clinical benefit rate was still 46% in platinum resistant patients.

Other Study Results:

> 50 patients participated in the study (13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval).

> 20 patients (40%) achieved complete or partial responses under RECIST (Response Evaluation Criteria in Solid Tumors) criteria and/or tumor marker (CA125) responses.

> 3 patients (6.0%) maintained RECIST disease stabilization for more than 4 months.

> Overall clinical benefit rate (complete response + partial response + stable disease) = 46%.

> Median response duration was 28 weeks.

> There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory patient subgroups (69%, 45%, and 23%, respectively).

> Analyses indicated associations between platinum sensitivity and extent of olaparib response


Aug 152010
 

Dear Parp Inhibitors Cancer,
What is Olaparib?

Olaparib is an inhibitor of the enzyme Poly ADP ribose polymerase (PARP). It was one of the first PARP inhibitors developed by KuDOS Pharmaceuticals that was later bought out by AstraZeneca. More specifically olaparib is an experimental drug that has been shown in studies to shrink or stabilize tumors in almost 50% of ovarian cancer patients possessing BRCA1 or BRCA2 mutations. Studies so far haven’t shown major side effects in people, but those who did have them reported some fatigue, somnolence, nausea, loss of appetite and thrombocytopenia.

In the most simplistic form of explanation, an olaparib operates by turning a tumor’s specific genetic defect against itself. In vulnerable cells, olaparib blocks the repair of naturally occurring breaks in the DNA, which healthy cells are normally able to repair. Thus the vulnerable cancer cells (considered those with an existing defect in a DNA repair pathway caused by a mutation in the BRCA1 or BRCA2 genes) are unable to repair themselves. Those cells then die.

Aug 132010
 

In a recent feature story on the use of Parp Inhibitors for the treatment of breast and ovarian cancer in women, Dr. Charles L. Vogel does a good job of explaining, in layman terms, what a Parp Inhibitor is and how parp inhibitors treat cancer. From the video:

What happens is when different chemotherapy drugs act on the DNA of a tumor cell, they cause damage. But the tumor cells are smart and they can repair that damage. Yet the PARP inhibitor is able to inhibit the ability of the tumor to repair that damage… if you can inhibit DNA repair then the tumor will be destroyed.

Here’s the full video…

Aug 112010
 

AstraZeneca stands to benefit greatly from the successful studies, to date, on the use of Parp Inhibitors in the treatment of cancer. The targeted treatment received mass publicity in June 2009 when a study came out showed great promise and results. So how did AstraZeneca become involved with parp inhibitors? In 2006, AstraZeneca acquired a privately owned UK-based pharmaceutical company experimenting with parp inhibitors in the treatment of cancer. The company, KuDOS Pharmaceuticals Limited, was bought for nearly $200 million. At the time, AstraZeneca put out a press release stating, in part:

“The acquisition of KuDOS Pharmaceuticals represents an important strategic step for AstraZeneca: strengthening its portfolio of promising cancer treatments from external opportunities and also demonstrating its commitment to discover, develop and bring to market innovative therapies.

This transaction provides AstraZeneca with a widely-recognised expert group and technology platform in an area of research that complements internal capabilities in oncology, one of the company’s key therapy areas. The DNA repair platform developed by KuDOS Pharmaceuticals, in association with its founder Professor Stephen Jackson of Cambridge University, includes several different approaches towards inhibition of enzymes involved in the responses to various types of DNA damage. DNA repair inhibitors have the potential to kill cancer cells either as stand-alone therapy or by enhancing the efficacy of chemo- and radio-therapies.”

Now AstraZeneca stands to profit nicely if the study of parp inhibitors continue to produce positive results. Parp inhibitors have been shown to stop tumor cell DNA from repairing itself when a patient goes through chemotherapy. That’s a vital step forward in the treatment of cancer. If further studies continue to back the initial results, then parp inhibitors will be considered one of the biggest breakthroughs in the treatment of cancer in decades. And AstraZeneca will be at the forefront of that movement, thanks to a purchase made in 2006 that is paying off big for AstraZeneca and for those hoping for advances in cancer treatment.

Aug 102010
 

In the video below, Dr. Ester Hammond (Gray Institute for Radiation Oncology and Biology), discusses her research of PARP inhibitors, suggesting that PARP inhibitor drugs can be used on a wide variety of drugs because of how it works. In one part of the video she says that the PARP Inhibitors “have a wider application. Specifically that they may be used to target cells in low oxygen conditions, which would apply to a much broader range of tumors…” Here’s Dr. Ester Hammond

Aug 092010
 

(Parp Inhibitors Research Video) Below we have posted for you a four part lecture series about Parp Inhibitors as presented by Dr. Stephen Lemon, who is a medical oncologist at Oncology Associates in Omaha, Nebraska. He also spends a good portion of his time educating people about cancer. The talk about Parp Inhibitors doesn’t start until four minutes and 30 seconds into the first video (we tell you that so that you can “fast forward” if you like). Up until then, Dr. Lemon talks about his Website and about why he wants health care reform (interjecting humor). Then he starts to talk about Parp Inhibitors with its application to breast cancer. It’s a four part video series (about 30 minutes in total) and we’ve posted all four parts for you below:

Part 1:

Part 2:

Part 3:

Part 4:

Aug 092010
 

Below is a video report that was created at the San Antonio Breast Cancer Symposium in late 2009. The video report talks about Parp Inhibitors and how this new class of compounds may dramatically increase the effectiveness of breast cancer treatments, among others. The video includes comments from Dr. James Ford of the Stanford University School of Medicine. Ford says, in part, “… Parp Inhibitors is really an entirely new pathway to targeting cancers that hasn’t been exploited before…” Parp Inhibitors should be able to aid in the treatment of a variety of cancers in the future, pending future trials. Here’s the video…

Aug 092010
 

(Parp Inhibitors Videos) In June 2009, a lot of stories began to break in the news about “Parp Inhibitors” and how they relate to the treatment of cancer. On June 24, 2009, the NBC Nightly News featured a story on Parp Inhibitors that began, “Now we turn to what some are calling the most important cancer treatment breakthrough in a decade.” The story talks about how a study featured in the New England Journal of Medicine, on Parp Inhibitors, is showing a lot of promise for the development of new drugs to treat cancer. The Parp Inhibitor trials were remarkable in the treatment of cancer. Here’s the story…