Attention on small molecule inhibitors – after being in the doldrums for a while – seem to be making a comeback over the last year with much attention focused on a few companies developing new selective agents in specialised niches.
Time for a KRAS spring clean!
One such space is KRAS inhibition. Not just in terms of direct or indirect inhibition, but also with regards to tackling acquired resistance mechanisms such as SHP2. While there has been quite the frenzy over what Amgen, Mirati, Revolution Medicine and a few others are all doing, other companies are quietly getting on with the business of producing some nice work and will soon be ready for the off.
In our latest review we explore some of the factors involved, which companies will need to be concerned about going forward, especially in the context of future combination strategies.
In solid tumours, with targeted therapies the winners are not always the ones who reached the market first, but rather the crafty ones who optimise the combination strategies and become ingrained in protocols across multiple situations.
Here we look at one of the hidden gems in the KRAS space and explore what it does, why it’s important and how it might fit in. We also include a company interview with a scientist who gets the broader implications…
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September 1st… as the hot summer floats away from London town and cooler autumn days draw in, it’s time to think about the upcoming fall cancer conference season – it’s quite a busy one this year!
In the coming weeks, I will be rolling out our series on the ESMO 2016 Previews (Twitter #ESMO16) and taking a more in-depth look at various topics of interest. The Copenhagen meeting is later than usual and also more compressed, with numerous sessions now held simultaneously. It used to be that you could take a break between key sessions, but not any more – there’s a lot going on this year.
One of the things that jumped out to me from a preliminary review of this year’s hectic ESMO program is an interesting novel target that had some early preclinical data at AACR, but that sadly got lost in the tsunami of data there.
It is good to have that reminder and be able to return to it in the context of broader data because overcoming barriers to drug resistance with targeted therapies is still an important issue that is worth researching.
You likely won’t see it in many analyst reports or previews, however, although it’s a hidden gem of great interest and well worth exploring in terms of what we know so far. This means that readers will be both prepared and intrigued – don’t be surprised to hear about some BD&L deals in this niche in the future.
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Today in the plenary session of the 102nd Annual Meeting of the American Association for Cancer Research (AACR), Lynda Chin from Dana-Farber Cancer Institute in Boston provided an excellent overview of the challenges and opportunities of translating insights from cancer genomics into personalized medicine that will benefit patients.
I unequivocally recommend listening to the webcast of the plenary when it is posted on the AACR website.
As Dr Chin stated at the start of her presentation, “cancer is fundamentally a disease of the genome.” The goal of all cancer research is to make progress with prevention, detection and cure.
In the plenary presentation she highlighted some of the successes that have come from understanding the genome e.g. the knowledge of BRAF mutation in melanoma led to the identification of a target and development of a new drug in 8 years. In addition to the development of novel therapeutics, genomics research has helped companies reposition drugs and she highlighted crizotinib as an example (move from C-Met to ALK inhibition in NSCLC).
These successes have “motivated researchers” according to Chin. However, it is transformative new technology such as the next generation of sequencing technology that has heralded “a new era of cancer genomics.” Massively parallel sequencing enables comprehensive genome characterization.
Not only has innovative new sequencing technology increased the throughput, but it has dramatically decreased the costs. As Dr Chin noted, some have questioned whether cancer genomics is worth it? She outlined some of the recent successes, such as BAP1 in ocular melanoma (see my previous post on this) as examples of its value.
Challenges remain such as the management of the vast amount of data that genome sequencing produces. Data management, processing and storage remain issues, as does the need to develop a reference human genome against which a patient’s tumor profile could be compared.
And even when you find a mutation, the challenge is to separate the “drivers” from the “passengers.” This according to Chin requires a “robust statistical framework”.
Cancer signaling is not linear, but is a highly interconnected and redundant network, so it remains a big task to translate genomics into personalized medicine. According to Dr Chin using mice as models to bridge the gap between sequencing and man may be the way forward in translating cancer genomics into personalized medicine.