A new fusion gene target in a rare soft tissue sarcoma

Posted on February 14, 2012 by MaverickNY

Every now and then my eye is caught by reports of new fusion genes being found in different cancers. Often these descriptions involve researchers across multiple laboratories due to the rarity of the target. Following a discussion on Twitter yesterday, a friend sent me the link to this interesting paper published in Science Translational Medicine. Naturally, one of the first things that came to mind was ‘is the identified target druggable?’

Source: wikipedia micrograph of epithelioid hemangioendothelioma (from the liver)

Tanas et al., (2011) used deep gene sequencing and conventional cytogenetics to identify two genes involved in chromosomal translocation in epithelioid hemangioendothelioma (EHE), a rare vascular sarcoma that arises out of endothelial cells, namely:

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The role of the Androgen Receptor in breast cancer

Posted on February 10, 2012 by MaverickNY

This week I have been in Orlando for the American Association for Cancer Research (AACR) Special Conference on prostate cancer chaired by Drs Arul Chinnaiyan (U. of Michigan) and Charles Sawyers (MSKCC). It was a superb meeting, probably one of the best I’ve attended since the PI3K meeting that AACR hosted in February last year. I wrote nearly half a Moleskine of notes that vaguely resemble chicken scratch – there were so many good talks that stimulated new ideas and explained a few scientific things I also didn’t know too well. Learning is a continuous lifetime experience, after all.

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Is ARN-509 (Aragon) potentially better than MDV-3100 (Medivation) in advanced prostate cancer?

Posted on February 2, 2012 by MaverickNY

Many readers will have noticed that the advanced prostate cancer market is rapidly becoming crowded with three new therapies (cabazitaxel, sipuleucel-T and abiraterone) already approved and several more in late stage development, including Alpharadin (radium-223) and MDV3100, both likely to file this year. In addition, others are focused on bone complications, such as denosumab, which is expected to have a tough ODAC meeting this month, and cabozantinib, a multikinase inhibitor currently in phase III trials.

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Update on Medivation’s MDV3100 in advanced prostate cancer

Posted on January 31, 2012 by MaverickNY

This weekend heralds the annual American Society of Clinical Oncology (ASCO) Genitourinary (GU) meeting in San Francisco, although ASCO held their press briefing today to provide an update on some of the key topics.

For those of you interested in Alpharadin (radium-225) in castrate-resistant prostate cancer (CRPC), check out the update of Dr Oliver Sartor’s presentation, which is covered on Biotech Strategy Blog.

The key topic that most interested me though, was Dr Howard Scher’s update on Medivation’s Androgen Receptor antagonist, MDV3100, in CRPC. Previously, Medivation announced that the data showed an improvement in median overall survival (OS) of 4.8 months and this is still solid (Note: J&J’s abiraterone was approved by the FDA based on an OS of 3.9 months in the same population and must be taken with prednisone).

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On KRAS, NF-kB activation and pancreatic cancer

Posted on January 31, 2012 by MaverickNY

Pancreatic cancer as many readers know, is one of those cancers that is generally diagnosed later than most in stage IV and as a result, has a poor prognosis, often only a year or so from diagnosis.

It has been known for a decade that constitutive Kras and NF-kB activation is one of the signature changes in the disease in the majority (80-95% ) of patients. Kras is a particularly important gene because it is often involved with on-off signaling of other genes. In addition, mutational inactivation of a key tumour suppressor gene (Ink4a/Arf) also occurs in over half (50-75%) of pancreatic adenocarcinomas. What is not known, however, is what are the key signaling pathways downstream of Kras and how they relate to pancreatic cancer.

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FDA approves Roche hedgehog inhibitor vismodegib/Erivedge in basal cell carcinoma

Posted on January 30, 2012 by MaverickNY

It’s been quite a roller coaster ride for Hedgehog inhibitors of late.

Last week, brought negative data as Infinity announced that their phase II trial with saridegib (IPI-926) had been stopped for futility in pancreatic cancer. This trial sought to determine the impact of the hedgehog in combination with gemcitabine over gemcitabine alone in advanced pancreatic cancer. Unfortunately, the trial was stopped for futility, meaning the control arm was doing better than the treatment arm.

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A new opportunity for vemurafenib in BRAFV600E colon cancer

Posted on January 26, 2012 by MaverickNY

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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Unravelling early colorectal cancer: the links between ROS, DNA methylation and inflammatory responses

Posted on January 24, 2012 by MaverickNY

During yesterday’s discussion with Dr Ray DuBois (MD Anderson Cancer Center) about inflammation and methylation, the topic of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) came up as you can see from the brief audio clip below:

Steve Baylin’s paper sounded most interesting, so I tracked it down – see O’Hagan et al., (2011) in the References below for the direct link.

CIMP is interesting to look at because it can occur in some 30% of colorectal cancer cases and has been previously shown to be an independent predictor of survival with 5FU in early or adjuvant CRC (van Rijnsoever, 2003). It is, therefore, a potentially useful molecular marker in this disease.

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New research demonstrates the link between inflammation and early development of colon cancer

Posted on January 23, 2012 by MaverickNY

Recently, epigenetics has been very much to the forefront with promising new human data in lung and breast cancers.

homecover New research demonstrates the link between inflammation and early development of colon cancer

Nature Medicine

This morning I was therefore thrilled to see some exciting work just published in Nature Medicine Online First from Ray DuBois’s lab at MD Anderson Cancer Center, on the potential role of inflammation and silencing of tumour suppressor genes in early colorectal cancer. Previously, the group looked at the role of COX-2 in intestinal inflammation and colorectal cancer and observed that:

“A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet and lifestyle are the risk factors for CRC.”

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ASH 2011 Update #2 – Non Hodgkins Lymphoma

Posted on December 21, 2011 by MaverickNY

I’ve been busy with other things offline since the last blog update from the American Society of Hematology (ASH) meeting in San Diego, but will be catching up on my notes from the conference over the next few days.

In addition, my colleague Pieter Droppert has already posted his topline impressions of the meeting on the companion Biotech Strategy Blog, which readers may be interested in:

Meanwhile, I thought it would be a good idea to look at the pipeline developments in non-Hodgkin’s lymphomas (NHL) that I particulalry liked at ASH:

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