Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘EGFR’

Transformative antibody technology in cancer research

Recently, I came across an exciting new development in a Nature publication and couldn’t resist teasing my Twitter followers with this terse statement:

Naturally, this mischievous tweet set off a lot of folks frantically trying to guess what I was referring to and the @replies came in thick and fast.

The National Science Foundation defines transformative as:

Overcoming drug resistance in lung cancer

On the final day of the annual 2013 meeting of the American Association for Cancer Research (AACR) in Washington DC, Jeffrey Engelman (MGH) hosted an excellent plenary session on “Cancer Evolution and Resistance” with a series of superb talks not only from himself, but also Neal Rosen (MSKCC), Todd Golub (Broad Institute) and René Bernards (Netherlands CI).

If this session is included in the webcast, I would highly recommend watching the whole thing several times, as it was one of the meeting highlights for me. Despite being on the very last day, the large hall was pretty packed and well worth waiting for. You can check availability of the AACR 2013 webcast talks here.

A new opportunity for vemurafenib in BRAFV600E colon cancer

There’s been quite a flurry of commercial news on the Pharma front this morning, with Amgen buying Micromet (whose leading product is blinatumumab in ALL) and Celgene announcing their acquisition of Avila Therapeutics who have a Bruton Kinase Inhibitor (BTK) AVL-292 in phase IB development for lymphomas, which was all the rage at the recent American Society of Hematology (ASH) meeting last month.

The big news for me today, though, wasn’t the commercial acquisitions but a gem of a paper relating to science and its significance for future cancer treatment.

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How a metabolic protein PKM2 may have a key role in tumorigenesis

This morning I was taking a breather from work to catch up on my Science and Nature reading.

320px Protein PKM2 PDB 1a49 How a metabolic protein PKM2 may have a key role in tumorigenesis

Source, Wikipedia: Pyruvate Kinase Muscle isoenzyme

There was a most intriquing Letter to Nature from Lu and colleagues at MD Anderson, describing how PKM2 (pyruvate kinase muscle) may not just have an established role to play in metabolism (via the Warburg effect in glycolysis), but how it may also have important non-metabolic functions in tumour formation and growth:

“Here we demonstrate, in human cancer cells, that epidermal growth factor receptor (EGFR) activation induces translocation of PKM2, but not PKM1, into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of b-catenin.”

Update on EGFR resistance in lung cancer: new directions

This morning I was reading a fascinating paper on lung cancer and one of my favourite proteins, CRKL, from the group of prolific lung researchers at Mass General, Dana Farber, MIT and the Broad Institute in Boston:

“Over-expression of CRKL in immortalized human airway epithelial cells promoted anchorage-independent growth and tumorigenicity. Oncogenic CRKL activates the SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways. Suppression of CRKL in NSCLC cells that harbor CRKL amplifications induced cell death.”

Cheung et al., (2011)

We also know that one of the mechanisms of resistance to gefitinib is over-expression of CRKL in EGFR-mutant cells by activating ERK and AKT signaling.

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Useful resource on new therapies for lung cancer

“You no longer need to sit through a chicken dinner to watch top oncology researchers run through slides on what’s new and exciting.

This non-small cell lung cancer edition of the Cancer Educators Slide Library allows you to take your iPad to the backyard, sit down in the sunset breeze and watch Drs John Heymach, Tom Lynch, Vince Miller, Tony Mok and course director Dr Roman Perez-Soler spin an amazing decade-long tale of research innovation and discovery that has fundamentally changed clinical practice.”

Amusing openings in emails always grab my attention!

The elusive mystery of KRAS and EGFR inhibitors in colorectal cancer

The other week during a conversation with Dr Gordon Mills (MDACC) at the European Multidisciplinary Meeting (EMCC) in Stockholm, he mentioned the conundrum of variable responses to EGFR inhibitors in colorectal cancers and the impact of RAS.  Originally, it was thought that patients who had wild type, but not mutated, KRAS were more likely to respond (see Allegra et al., 2009 in the references below).

The reality, however, is that variable responses to therapy have actually been reported by several groups with cetuximab and panitumumab. De Roock et al., (2010) reported better outcomes with cetuximab in patients with p.G13D-mutated tumours than with other KRAS-mutated tumours, contrary to the US and EU Guidelines, so the situation is clearly more complex than first thought.

Making a Difference: an interview with Dr Gordon Mills

Earlier this year, I announced that there were two people I was hoping to interview next as part of the ongoing Making a Difference series, where thought leaders share their ideas and vision on emerging and important topics in cancer research. Previous discussants have included the following:

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New developments in the biology pancreatic cancer

At the American Association for Cancer Research (AACR) Second Frontiers in Basic Cancer Research Conference this week, two interesting presentations on pancreatic cancer caught my eye. It has long been my belief that we will see no major breakthroughs for this devastating disease until our understanding of the biology advances.

Here’s a quick snapshot of each one:

EGFR Essential for the Development of Pancreatic Cancer

Barbara M. Gruener, a researcher at the Technical University in Munich, Germany stated that,1

“Originally, we wanted to characterize the known role of EGFR in pancreatic cancer to a higher extent so that EGFR targeted therapy could be more individualized.”

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New solutions for resistance to therapies in lung cancer?

One of the things that is both frustrating and fascinating is the development of resistance to therapies in cancer treatment.  By this, I mean clearly it’s not something we want to see from a patient or physician perspective and if possible, to delay it as long as feasible.  On the other hand, the mechanics behind the biology of drug resistance is a fertile field for curious scientists.

I never fail to feel a sense of awe when a group cracks open new mechanisms that improve our understanding of cancer.  It is, after all, a highly complex and fickle topic. I’ve often wondered why is it that some patients see resistance set in early and others do not? Why does resistance occur, period?

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