We now turn our sights to targeted therapies and DNA Damage Repair (DDR). This is an important topic that has seen much focus in ovarian cancer of late and will likely see renewed interest in breast cancer at the forthcoming ASCO meeting next month. As we segue from one set of conference coverage to the next, there is inevitably going to be overlap, which is a good thing here as it helps with background and preparation in getting up to speed.
There is no doubt that DDR has had a bit of chequered history over the last decade, whether it be the spectacular (and sadly predictable) flop of Sanofi’s iniparib in triple negative breast cancer (TNBC), the negative ODAC incurred by AstraZeneca’s olaparib in ovarian cancer, or AbbVie’s more recent veliparib failures, to the much more positive events such as three PARP drugs now approved in different lines of therapy in ovarian cancer (olaparib, rucaparib and niraparib).
If ever there was a niche for the roller coaster ride that is oncology R&D, it has to be PARP inhibitors. There’s much more to DDR than just PARP though.
Indeed, there are multiple intriguing targets to explore and also the potential for combinations with cancer immunotherapy approaches that may yield encouraging results in the future.
Can we go beyond ovarian cancer into other tumour types and if so, which ones look encouraging and how woluld we go about exploring those idesa? What makes one approach more successful than another?
Here we explore the world of DDR through the lens one company’s approach and look at what they’ve done, where are they now and where they hope to be. It certainly makes for an intriguing and candid fireside chat.
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Dr James Gulley is Chief of the Genito-Urinary malignancies branch and Director of the Medical Oncology service at the National Cancer Institute (NCI) in the National Institutes of Health. He’s a world-leading GU cancer expert and at the forefront of pioneering research to make cancer immunotherapy work in prostate cancer.
We last spoke to him at ASCO 2015 (See post: The future of prostate cancer immunotherapy). You can listen to excerpts from this interview on Episode 4 of the Novel Targets podcast (See: The non-inflamed tumour show).
Almost two years on, and new research by Dr Gulley and colleagues from the NCI shows that the STING pathway may have an important role to play in prostate cancer immunotherapy. Activation of this pathway through a novel mechanism could turn a cold non-inflamed tumor into a more inflamed or hotter one in men with advanced prostate cancer. How cool is that?!
At the 2017 annual meeting of the American Association for Cancer Research (AACR) that was recently held in Washington DC, Dr Gulley graciously spoke to BSB about some of the novel trials that are underway at the NCI, with the aim of making cancer immunotherapy work in men with advanced prostate cancer.
Dr Jim Gulley, NCI at AACR17
This is the seventh expert interviews in our series from AACR17 where we explore the conundrum:
How does Dr Gulley plan to light the immune camp fire in prostate cancer?
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Following the recent approval of Clovis’s rucaparib (Rubraca) by FDA under priority review as monotherapy for the treatment of women with certain types of advanced ovarian cancer, then impressive SOLO-2 maintenance data after initial chemotherapy at SGO earlier this month, PARP inhibitors continue to be in the news.
There’s always more though!
This afternoon saw the approval of Tesaro’s PARP inhibitor niraparib (Zejula) by the US Food and Drug Administration (FDA) for maintenance treatment of women with ovarian cancer who are in a complete or partial response to platinum-based chemotherapy (Link to label).
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The recent PARP inhibitor data has stirred up a lot of interest amongst BSB subscribers (See post: PARP! PARP! what’s hot in ovarian cancer at SGO and AACR?).
So, rather than do another AACR 2017 Preview (more coming next week!), it seemed timely to take a look at some of the interesting questions we’ve received from subscribers.
Five questions have been selected for answer in this week’s BSB reader Q&A. We don’t award prizes if your question is selected, nor do we name who asked the question, but everyone benefits when interesting questions are asked and we can all learn from each other.
As author Thomas Berger aptly said:
“The art and science of asking questions is the source of all knowledge.”
What differentiates many world class cancer researchers is frequently the scientific questions they ask in their work. The same holds true if you are a C level executive or a journalist. The quality of the answer you obtain is often dependent on the quality of the question you ask.
We hope that being better informed about the issues and topics we write about on BSB will enable subscribers to ask better questions, and in the process make better decisions.
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There’s no secret or surprise with our latest AACR Preview as this week the focus takes a slight turns or detour to the annual meeting of the Society for Gynecology Oncology being held in National Harbor, Maryland.
PARP inhibitors in ovarian cancer have been a hot topic since last autumn when the PARP inhibitor data dropped at ESMO in Copenhagen, and was not without controversy either.
We’ve been following the trials, tribulations and even machinations, of the clinical development of olaparib, rucaparib and niraparib for a while now so what’s in store in the latest round of salvoes?
And importantly, what else can we expect to see in DC at AACR next month?
For a tumour type that hasn’t received much attention over the last decade or two, things are distinctly picking up. Is it all good though?
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HI Koko Crater Flowers
Over the last week or so, we’ve received a lot of questions on the following topics relating to women’s cancers in breast and ovarian carcinomas:
- APHINITY impact – pertuzumab and neratinib
- PARPs in ovarian cancer – niraparib, rucaparib and olaparib
- Seattle Genetics and Immunomedics
So this is probably a good time for a February BSB Reader Q&A post on the hot topics of the moment in cancer research.
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The huge pile of interesting scientific papers yet to be read seems to breed overnight and one constantly feels like they’re 2,000 articles behind, even with spending Friday mornings attacking them with gusto.
This was as true in my PhD days as it is now. For a scientist, these represent a lifeline and an important necessity, rather than a luxury.
In the last journal club posting we covered some hot topics in cancer immunotherapy, so this one covers a very different topic, namely targeted therapies.
It’s a good time for a new journal club post, where we tackle some of the recent published literature in oncology and highlight some important new findings that could have an impact on cancer research and development.
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Today we continue the second of a two part interview with a global thought leader who is also a scientist-clinician and well versed in cancer research as well as clinical trials.
Old Town Hall, Munchen
We explore how we can do clinical trials better in order to learn via a more rigorous process what works, what doesn’t, and why. After all, we we don’t know why certain approaches didn’t work or what the mechanisms of resistance are, how can we possibly improve?
Randomness is not necessarily a good thing in clinical research, especially if you don’t know what target you’re actually trying to hit!
If you missed the first part of this latest KOL interview and want to catch up then you can find it here (Link).
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Part 3 of our series on Gems from the Poster Halls at ESMO continues with a look at another four important combination studies that may be of keen interest to readers.
These include both targeted therapies as well as immunotherapies.
Some of the posters I was originally keen to write about turned out a little unexpectedly with some issues to address i.e. lack of efficacy or unwanted toxicities based on the dosing schedule used and may require tweaking of the dosing, schedule or trial design. Others will unfortunately be destined for dog drug heaven unless a new tumour type offers more promise. Such is the R&D roller coaster that is oncology – sometimes we forget that more compounds fail than make it market.
The good news is that there were plenty of promising approaches that are worthy of writing up and discussing. In the third part of our poster mini-series, we take another deeper dive with a careful look at some new data in Copenhagen.
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One of the surprising things I learned over the summer was how many people misunderstand how advanced ovarian cancer is treated as a disease… it isn’t really one disease to start with, but is actually a series of subsets depending on the molecular underpinnings and also how women with the condition react to therapy.
Imagine then, when we see a series of press releases and abstracts emerge on PARP inhibitors followed by a rather indecent and sudden rush to judgment by Wall St and investors on the ‘Winner takes All’ out of the lot?
Except that real life doesn’t work that way in clinical practice.
A head/desk moment to be sure, and a frustrating one for those who understand what this is actually all about. To address this siituation, we had the pleasure of communicating with KOLs remotely or sitting down with several thought leaders in gynecologic cancer in Copenhagen to debate various aspects relating to current treatment paradigms, new clinical trial data with PARPs, and what they are most excited about going forward.
Today’s post highlights our latest thought leader interview with an experienced GYN oncologist and their perspectives on the rucaparib and niraparib data presented earlier this month at ESMO.
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