It amuses me to realise that I’ve been writing about and following PARP inhibition since 2006 or so, when the field was in that twilight zone of early drug development between preclinical and clinical, thus just beginning to hit some sort of consciousness and broader interest in cancer research.
The AACR Molecular Targets meeting in 2009 was the first scientific meeting I covered as a science writer on the old Pharma Strategy Blog, which focused on early drug development from preclinical to phase 2 – after that I would rapidly lose interest and move on to the next new shiny scientific lure to research and discuss. No doubt this eager new writer ran about like an overenthusiastic little puppy in the poster halls chatting to scientists about their research, much to the amusement of the more staid press room, who at that time probably never ventured out of the darkened basement gloom.
In one of the press briefings there, I met an engaging and thoughtful scientist who was presenting his poster on PARP and synthetic lethality. He kindly took the time to explain in plain English a commonsense analogy that was most helpful for grasping complex concepts. Having sat through several long talks from luminaries in the field such as Drs Hillary Calvert and Alan Ashworth that covered double strand breaks and DNA repair mechanisms, it was a most welcome respite in the hurly burly of the conference!
Imagine his imagery…
You have a four legged coffee table or wooden chair and one of the legs breaks off or is damaged. The table remains standing, albeit less stable than before. Now a second leg breaks, and inevitably, the table is so unstable that it falls over.
Once you grasp that simple analogy for synthetic lethality, you have the basic idea of DNA double strand breaks and how inefficient repair can lead to vulnerabilities in the tumour that can be exploited.
The scientist I spoke to in Boston back in 2009 was Dr Mark O’Connor.
He was involved in DNA damage response research at a little known private company in Cambridge, UK called KuDos, who were subsequently acquired by AstraZeneca. Nearly a decade on and Dr O’Connor is still at the company; he now heads up their DNA damage response area.
Dr Mark O’Connor, AZN
With olaparib (Lynparza) since approved by the FDA in ovarian cancer and slated for the ASCO 2017 plenary session for HER2- breast cancer, things have certainly changed a lot since those early heady days of KuDos and the R&D journey has not been without its notable ups and downs along the way.
In Chicago earlier this month, I had the pleasure of catching up again with Dr O’Connor to learn more about the journey, and importantly, where things are going next. It’s quite an interesting roller coaster ride, to be sure!
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Often times when we see promising data presented at a cancer conference, we interview a thought leader and post the expert opinion with additional commentary and insights.
ASCO17 OlympiAD Plenary
At ASCO, we decided to take a different approach, a twist on the usual fare… given that two of the phase 3 trials, OLYMPIAD and APHINITY, received significant attention and focus involved breast cancer, we reached out to numerous experts and curated their sentiments on both studies. For completeness and fair balance, these included industry and academic opinions.
Today, we begin with the OLYMPIAD trial presented by Dr Mark Robson on behalf of his colleagues exploring the role of the PARP inhibitor, olaparib (Lynparza), in HER2-negative metastatic breast cancer with germline BRCA mutations.
There’s a lot to consider here, not least is where do we go next from here and which PARP combination approaches are researchers most excited about?
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Yesterday Novartis announced the initial data from the JULIET trial in relapsed/refractory aggressive lymphomas such as diffuse large cell lymphomas (DLBCL) that were presented at the upcoming International Conference on Malignant Lymphoma (iCML) meeting in Lugano.
Here at BSB, we’ve been following CAR T cell therapy developments in earnest since 2012 when Penn and Novartis first announced their collaboration to develop what is now known as CTL019.
Five years on, we now have two such cell therapy products already filed with the Health Authorities and the JULIET trial will likely be the third indication submitted by the end of the year. This niche is now well established for regular readers and not something that has been a flash in the pan over a year or so.
There are a few interesting points of note on the CAR T cell front that are also worth exploring in conjunction with this news.
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Chicago: Greetings from Peets Coffee in UIC Halstead where we finally take a moment to stop, catch a breath and reflect on the tsunami of data being presented at the McCormick centre over the last couple of days.
Without much ado, here’s our review of new trends, highlights and lowlights from ASCO17.
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Right now many people are overwhelmed not just with the sheer number of ASCO abstracts to process and assimilate, but also the breadth and depth of the topics being covered.
This means that it’s time for some perspicacity… making sense of the data in order to look at the patterns and insights that are emerging.
In today’s preview, we identify some key strategic themes and offer a framework so that examples can be easily slotted into some semblance of order.
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Whenever one attempts to do a top 10 list of almost anything, there will inevitably be fans and detractors in equal measure and this BSB list is likely to be no different in that respect!
This week’s Fun Friday post highlights some important abstracts to watch out for in advance of ASCO 2017, so without much ado about nothing, you can check out our selections, some of which are likely to be controversial.
As usual, we also explain why they are important and what lessons can be learned.
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Although ASH and ASGCT are important meetings for CAR T cell therapies, there are still some intriguing data to be had at ASCO next month, including both oral and poster abstracts.
In our latest ASCO 2017 Preview, we take a look at what to expect from in the CAR T cell space.
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If there’s one topic that has generated a LOT of questions from BSB readers this month it is Puma Biotech’s neratinib in adjuvant breast cancer.
The FDA briefing documents came out yesterday and that started another flurry of ‘what do you think of them?’ style questions so here goes. I will say that while many are eulogizing ‘benign’ or ‘friendly’ on close reading and studying them, I’d say caveat emptor.
Things are not always what they seem.
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Contemplation in Chicago ahead of #ASCO17
As part of our ongoing American Society of Clinical Research (#ASCO17) Preview series (we’re on number 5 already), we turn our attention to an upcoming area of cancer research that is expected to play an important role in future clinical trials and combination regimens because of the mechanism of action involved.
It may also turn out to be a very handy and important approach for turning cold into hot tumours.
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As we all wearily trawl through the huge mountain of data for ASCO 2017, what stands out – and more importantly – what matters and why?
Before we get into our in-depth coverage based on the tumour type, target and modality landscapes, I wanted to take a moment to highlight five key abstracts that stood out for me as worthy of checking out in more detail once we get to Chicago.
Interestingly, only one of them is from big Pharma!
At least one had some negatives associated with it as we’re not all happy clappy everything is great enthusiasts here at BSB. We do try to be fair minded and objective as possible about data.
So what’s in store and why do these five matter?
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