Cancer Clinical Trials: Companion Diagnostics or Gene Sequencing?

Posted on February 21, 2012 by MaverickNY

Last year saw some interesting developments from MD Anderson Cancer Center in early phase clinical trials that may have a far-reaching impact on the future of cancer research as we know it:

At ASCO in June, Dr Tsimberidou presented the initial results from a phase I study run by the MD Anderson Department of Investigational Cancer Therapeutics group. Instead of testing patients with a given cancer (eg lung) for individual mutations eg ALK or EGFR and then offering patients a targted drug as we normally do, they ran a broad diagnostic panel across a multitude of patients with different cancers to determine what the tumour was telling them about the aberrations and selected appropriate targeted therapies. While the study was small in size, the results were better than random selection.

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Raised platelets reduce survival in ovarian cancer

Posted on February 15, 2012 by MaverickNY

During my years in Pharmaland, I often sat in waiting rooms waiting to see the Principal Investigator (PI) for one of the studies we were doing. I would generally see them at the end of the clinic, preferring to arrive early and chat with some of the patients to learn of their experiences, the trials and tribulations of cancer therapy. This keeps your feet on the ground – drug development is not an academic exercise, there are real people involved after all.

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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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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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miRNA as a potential biomarker for early breast cancer

Posted on January 16, 2012 by MaverickNY

One way to potentially improve long term cancer statistics is earlier detection, and in high risk patients, appropriate initiation of earlier treatment, since it is well known that the survival in stage II or III breast cancer is noticeably better than that for stage IV metastatic disease.

A critical question then, is how do we improve earlier detection?

There are a number of ways to achieve this:

Imaging techniques
Prognostication
Diagnostics
Biomarkers

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Gene mutation and resistance to chemotherapy in colorectal cancer

Posted on January 5, 2012 by MaverickNY

This week’s New England Journal of Medicine (NEJM) contained a fascinating article on how a specific gene mutation known as Transcription factor AP-2 epsilon, TFAP2E–DKK4, appears to be responsible for inducing at least some of the resistance to chemotherapy that occurs during treatment of colon cancer.

At first sight, I wasn’t sure from the abstract if they were referring to either adaptive resistance to therapy or whether genetic changes already present limited the effectivenes of the treatment.

Further reading of the full article more specifically pointed to the latter:

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AVEO announces front-line data in renal cell cancer for tivozanib

Posted on January 3, 2012 by MaverickNY

A very happy New Year everyone! After shaking off the dust of an extended break over the last two weeks, this morning brought plenty of news to kick start 2012.

The most interesting news was AVEO-Astellas’ announcement regarding their VEGF inhibitor, tivozanib, in advanced renal cell cancer (RCC):

“Tivozanib demonstrated superiority over sorafenib in the primary endpoint of progression-free survival (PFS) in TIVO-1, a global, randomized Phase 3 clinical trial evaluating the efficacy and safety of investigational drug tivozanib compared to sorafenib in 517 patients with advanced renal cell carcinoma (RCC).”

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What’s hot at SABCS – Update 2 – advanced breast cancer

Posted on December 10, 2011 by MaverickNY

After a number of basic research and science sessions over the last two days (see the Update 1 post on the science that intrigued me for more details), but the last two days heralded some excellent clinical sessions, in both oral and poster forms. These included the presentation of the much anticipated update to the BOLERO-2 trial, which was also published in the New England Journal of Medicine online and the CLEOPATRA study, also published in the same journal. One of the more impressive posters that caught my eye was the ENCORE 301 study, which provided an update to the entinostat data in ER/PR+ HER2- advanced breast cancer.

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What's hot at SABCS – Update 1

Posted on December 8, 2011 by MaverickNY

Yesterday evening brought a flurry of news around the New England Journal of Medicine articles for the BOLERO2 and CLEOPATRA trials, but out of respect to the presenters, I hate talking about the actual data before its being presented. Call me old fashioned if you like, but it seems odd moving up deadlines for the publication ahead of the presentations instead of releasing them on the day and is a little disrespectful of the journal towards the presenter and attendees.

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