Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘AKT’

ASCO 2012 Preview – Highlights of key data emerging from Chicago

By on May 15, 2012

It’s that time of the year again where we cogitate and contemplate on what might be hot at the annual meeting of the American Society of Clinical Oncology (ASCO) before the abstracts are available (they’re released online tomorrow at 6pm ET).

This year, while interesting early data from up and coming small biotechs is likely to be eagerly presented in poster sessions, the focus is more likely going to be on big Pharma with various phase III and also late phase II trials that are due to report data.  Unfortunately, not all of these will produce overwhelmingly positive results though!

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Will combining custirsen and MDV3100 reduce resistance in advanced prostate cancer?

By on February 26, 2012

EAU 2012 View of Eiffel Tower 224x300 Will combining custirsen and MDV3100 reduce resistance in advanced prostate cancer?

Sights of 2012 EAU Congress

Greetings from the European Association of Urology (EAU) congress in Paris. Despite the grey drizzle typical of Europe in winter, this is actually quite an interesting meeting with lots of poster presentations.

One poster that caught my eye yesterday was from Martin Gleave’s group on clusterin knockdown synergising MDV3100 activity. Previously, we discussed on this blog how inhibiting clusterin with custirsen (OGX-011) potentiated docetaxel. At the AUA meeting last year, the issue of whether the same would happen with MDV3100 was suggested, as you can see in the short video blog.

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EGFR activates mTORC2 in glioblastoma – a potential role for new therapies

By on December 1, 2011

One of the great things about following the American Association for Cancer Research (AACR) on Twitter, is that they regularly share technical open access articles from their journals for scientists to read.  Of course, many will have access through their institution subscription, but there are also probably quite a few interested community oncologists and scientists like me that don’t. The idea of sharing some of their really important scientific research with the broader public is a great one – a little bit of goodwill goes a long way and furthers their cause too.

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Update on EGFR resistance in lung cancer: new directions

By on October 25, 2011

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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Update on MEK and AKT inhibition in RAS driven cancers

By on October 3, 2011

A couple of interesting developments have emerged over the last week with AKT and MEK inhibitors, specifically Merck’s MK-2206 and AstraZeneca/Array’s AZD6244, that are well worth discussing.

  1. At the ECCO/EMCC meeting in Stockholm last Tuesday, Johann De Bono discussed the combination data for MK-2206 and AZD6244 in KRAS driven colorectal cancer.
  2. Later the same week, Array Biopharma announced the initial results from a randomized phase II placebo-controlled study that compared the efficacy of selumetinib (AZD6244/ARRY-886) in combination with docetaxel compared to docetaxel alone in the second-line treatment of patients (n=87) with KRAS-mutant, locally advanced or metastatic non-small cell lung cancer (NSCLC).
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On mTOR and Tuberosis Sclerosis Complex (TSC)

By on July 26, 2011

It’s that time of year in the dog days of summer when many people in the industry are either incredibly busy, heads down, rolling out new things for the third quarter or else it’s a pleasant lull between the strategic and tactical phases and a good time to catch your breath.  Here in the Icarus office, we’re busy creating and writing a new series of syndicated reports in a variety of different tumour types and pathways.  I have hundreds of snippets and notes saved electronically from various cancer meetings this year, making it a great opportunity to collate and process them into broader insights. If you have any particular needs in this area, now is a good time to let us know, so do email me and your wishes may get added to the list.

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New mechanisms of resistance to MET inhibition

By on April 12, 2011

A very apt quote from Jeff Engelman’s group caught my eye this week:

“Unfortunately, cancers invariably develop resistance, and overcoming or preventing resistance will ultimately be key to unleashing their full therapeutic potential.”

MET is the receptor tyrosine kinase for hepatocyte growth factors (HGF) and inhibition has been implicated in metastases and migration of cancer cells (Rong et al., (1994), Takayama et al., (1997)), but more recently, it has also been observed that some tumour types have MET oncogenic addiction, including gastric cancer (Smolen et al., 2006).

6603884f3 New mechanisms of resistance to MET inhibition

MET Inhibition - source: Ma et al., (2007) BJC

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Elements of success in cancer research

By on March 10, 2011

“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

170px Jordan by Lipofsky 16577 Elements of success in cancer research

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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Molecular subtypes in gliomas predict prognosis

By on March 1, 2011

One of the hallmarks of cancer is that even within different tumour types, there is an enormous degree of heterogeneity. Ultimately, in simple terms this means that individual patients will respond to different therapies depending upon their underlying biology.   The challenge, therefore, is defining and categorising the subtypes and working out which are the passenger and driver oncogenes, since the latter will cause aberrant tumour growth and survival, while the former may result as a consequence of changing pathway activity.

This morning I was researching gliomas and came across this old paper (March 2006) that looks at molecular subtypes of gliomas i.e. glioblastomas and astrocytomas.  The article concluded:

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PLX4032 phase III data in metastatic melanoma announced by Roche

By on January 19, 2011

Some of the most frequently searched words on this blog or those that arrive via organic Google searches centre around:

  • Melanoma
  • Ipilimumab
  • PLX4032

Interestingly, few are searching for RG7204, the Roche code for their compound being developed in partnership with Plexxikon or BRAF, the actual kinase target involved.

As background, you can read up on the past developments with BRAF V600 mutated melanoma here, here and here, including the phase II NEJM data, mechanisms of resistance (MEK or AKT) and how targeting CRAF as well as BRAF can lead to the development of squamous cell lesions in some patients.

This is a preview of PLX4032 phase III data in metastatic melanoma announced by Roche. Read the full post

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