Category Archives: New products

nab-Paclitaxel and its potential role in pancreatic cancer

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Back in 2009 at the American Association for Cancer Research (AACR) Molecular Targets meeting, a researcher (Anirban Maitra) from Boston had a most interesting poster about the use of nanotechnology to deliver nab-paclitaxel (Abraxane) to pancreatic adenocarcinomas in a more targeted fashion.  You can read about it in more detail from the meeting coverage at that time.

Essentially, one of the things that stops chemotherapy being more effective in advanced pancreatic cancer is that the stromal layer forms a physical, almost impenetrable layer, that slows drugs from getting through to the tumour.

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Video Report from 2012 European Association of Urology Congress in Paris

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Amazingly, it’s been a year since I started doing conference highlight videos, with the first one rolling out at EAU meeting in Vienna last March. They’ve proven to be much more popular than expected! The good news is that the video recording, production and presentation skills have improved along the way.

Unlike last year, the 2012 EAU Congress wasn’t lit up with excitement about new data (abiraterone and MDV3100 dominated last year).  Instead, there were more reflective discussions about how to consider sequencing and combinations in a more crowded castrate resistant prostate cancer market going forward as well as some mention of new up and coming targets outside the androgen receptor (AR) such as ERG and Src.

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The challenge of prostate cancer drug approval versus reimbursement

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IMG 7619 300x224 The challenge of prostate cancer drug approval versus reimbursement

Scenes from EAU - Arc de Triomphe

Here at the European Association of Urology (EAU) congress in Paris, there are some interesting debates amongst delegates attending the meeting regarding new therapies either recently – or about to be approved – for castrate-resistant prostate cancer (CRPC).

For example:

  1. How should abiraterone and MDV3100 be sequenced pre or post chemotherapy?
  2. Would combining the two drugs post chemo be a better strategy that leads to superior outcomes?
  3. Where does chemotherapy fit into this emerging paradigm?  Do we need chemotherapy in an new era of oral therapies?  If yes, which patients should be considered eligible?
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Combined VEGF and MET inhibition in some cancers may be better than either alone

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A couple of recent controversies in the field of angiogenesis have fascinated scientists and clinicians alike, namely:

  • Does VEGF inhibition lead to more aggressive tumours?
  • What drives metastases and invasion?
  • What is the role of tumour hypoxia in this process?

Data was originally presented in glioblastoma by Rubenstein et al., (2000), showing that anti-VEGF antibody treatment prolonged survival, but resulted in increased vascularity caused quite a stir.  Several other groups subsequently demonstrated in preclinical models that VEGF signaling shrinks tumours, but also results in increased invasion and metastases (see Casanovas et al., (2005), Ebos et al., (2009), Paez-Ribes et al., (2009), for examples).

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Cancer Clinical Trials: Companion Diagnostics or Gene Sequencing?

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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:

  1. 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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A new fusion gene target in a rare soft tissue sarcoma

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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?’

600px Epithelioid hemangioendothelioma EHE.Image5 A new fusion gene target in a rare soft tissue sarcoma

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

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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?

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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

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

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

infinity logo FDA approves Roche hedgehog inhibitor vismodegib/Erivedge in basal cell carcinomaLast 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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