Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘PI3-kinase’

Here’s a quick update on the next conference I’m planning to attend in New York next week.  It’s hosted by the New York Academy of Sciences (NYAS) in their downtown New York headquarters by the World Trade Center, which has fantastic panoramic views of uptown Manhattan and Brooklyn from the 40th floor.  More importantantly though, judging by the last few meetings I’ve attended there on cancer metabolism and a most fascinating lecture on ink and tattoos from Carl Zimmer, it should be a very good event and well worth attending.

While thoughts have already turned to the forthcoming ASCO 2012 meeting and today I am off to AUA 2012 in Atlanta, the annual meeting of the American Association Association for Cancer Research (AACR) last month continues to generate insights.

At AACR I was delighted to meet up with Philippe Aftimos, MD, a Clinical Research Fellow at the Jules Bordet Institute in Brussels, Belgium.   Philippe is medical coordinator of the Clinical Research Unit and someone who I met through social media (@aftimosp), so it was a pleasure to meet in person.

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“I’ve missed more than 9000 shots in my career.  I’ve lost almost 300 games.  26 times, I’ve been trusted to take the game winning shot and missed.  I’ve failed over and over and over again in my life.  And that is why I succeed.”

Michael Jordan, Chicago Bulls

Michael Jordan, Chicago Bulls

Source: wikipedia

Continuing the sporting metaphors this week, I was catching up on blog reading last night and noticed that Jim Lefevere put up a nice post on Digital Strategist about how:

Domain Expertise + Work Ethic + Time = Success

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Today, I’m heading off to San Francisco for the AACR Special Conference on Targeting PI3-Kinase and mTOR in cancer.  For those of you needing a brief primer on the pathway, you can find more about it in this 2010 post, which vies with one about ipilimumab in melanoma as the top two posts on Pharma Strategy since the end of October.

You can view the PI3K-mTOR program here.

I’m really excited to be attending this event – a lot of the ‘big guns’ in the PI3-kinase field are speaking at this event, including Lewis Cantley, Jeffrey Engelman, David Sabatini, Carlos Arteaga, Neal Rosen, Gordon Mills and many others.

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Over the last couple of years, our knowledge and understanding of non-small cell lung cancer (NSCLC) has improved as mutations and translocations that drive tumour growth and survival have been identified.

Unfortunately, while we have many new targeted agents in the clinic, few have so far made it to market for broader use in every day clinical practice.  EGFR inhibitors such as erlotinib (Tarceva) and gefitinib (Iressa) were probably the first to gain people’s attention and soon we will hopefully have crizotinib for ALK translocations, since Pfizer have begun the rolling NDA submission to the FDA.


"LKB1 is a master kinase"

What a great subheader in a paper last year by Reuben Shaw (journal link below).

Liver kinase B1 (LKB1) first got my attention at the AACR lung cancer meeting in San Diego earlier this year, when a couple of translational researchers mentioned it during informal discussions about how it might play a critical but subtle role in lung cancer and potentially other cancers.

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Last week there was lot of excitement and interest surrounding the blog post on Roche/Plexxikon's data on PLX4032 in metastatic melanoma published in the New England Journal of Medicine. A number of the discussions on Twitter and email centred around what is causing resistance to the BRAF inhibitor?

If we take a look at the BRAF pathway alone, we would get a sense of the flow from the PDGF ligand through RAS, RAF and MAPK, which essentially drives angiogenesis and proliferation, like this 2004 review article:

Picture 5
Source: Nature Reviews Cancer


One of the interesting things about scientific conferences such as AACR and ASCO is that everyone looks at the same data differently as if it were through a kaleidoscope.

Brand marketers focus on their competition by tumour type or disease, scientists look at specific mechanisms or pathways, investors look at particular companies and so on. 

Someone asked me the other day how I analyse the data.  I hadn't really thought about it much until then, but on reflection what I'm interested in is trends and how research evolves from a big picture science view so that means I look at pathways like a true biochemist.  This also teaches us where the gaps are and what opportunities may arise in the future.  It's not exactly rocket science, but it is a useful approach sometimes.

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There are a lot of clinical trials out there right with tyrosine kinase inhibitors; unfortunately many will fail because they were rushed into phase II or III trials without thinking through all the options.  There are, however, some smart companies out there who do think.

What was noticeable at AACR this year, was the surfeit of posters and presentations regarding logical combinations designed to eliminate escape routes and hence resistance.  For example, cross-talk is a common problem between ligands, eg IGF-1R and EGFR, so combining the two may reduce the problem but that isn't the whole story.


As many readers here on PSB know, I've not been a big fan of genome-wide molecular profiling, preferring an oncogene addiction approach to drug development and targeted cancer therapies. However, every once in a while something comes along that stops you in your tracks and makes you think differently.

This morning I was reading the latest copy of the New England Journal of Medicine over coffee and was fascinated by a review article by Drs Lenz and Staudt at the NCI on the molecular genetics of diffuse large-B-cell lymphomas (DLBCL), which account for 30-40% of newly diagnosed lymphomas.

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