Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Molecular Cancer Therapeutics’

It’s been a bad week for vitamins, especially with the publication of data from the SELECT trial that showed healthy men taking 400 IU/day of Vitamin E had a 17% increased risk of prostate cancer.

However, there is some evidence in support of tocotrienols (unsaturated form of Vitamin E) having a potential role to play in anti-cancer therapy.  One paper that caught my attention was the work by Kazim Husain and colleagues from the Moffitt Cancer Center and Research Institute in Tampa.

Published Online First (October 4, 2011) in the American Association for Cancer Research (AACR) journal, “Molecular Cancer Therapeutics” they showed that δ- tocotrienol may have potential to improve the effectiveness of gemcitabine in pancreatic cancer.

In their laboratory and animal based research, the authors showed that δ-Tocotrienol:

  • “augments inhibition of pancreatic cancer cell proliferation by gemcitabine”
  • “augments gemcitabine-induced apoptosis in pancreatic cancer cells”
  • down-regulates constitutively activated NF-κB in gemcitabine-treated pancreatic cancer cells”
  • “enhances the in vivo therapeutic effects of gemcitabine in a pancreatic tumor model in SCID nude mice”

Pancreatic cancer patients have a poor prognosis with less than <5% of patients surviving 5 years.  Current treatment revolves around the chemotherapy gemcitabine, but as the authors note in their Molecular Cancer Therapeutics paper, “tumor resistance is common.”

Various researchers are working on how to improve treatment options for pancreatic cancer.  One company I’m watching is AB Science and their phase 3 trial for masitinib.  You can read more about this on Pharma Strategy Blog and Sally Church’s excellent interview with CEO, Alain Moussy.

The work on the δ-tocotrienol form of Vitamin E shows that it may have a role to play in cancer treatment, notwithstanding the negative data that was published earlier this week in prostate cancer.

Husain and colleagues from Moffitt showed for the first time that δ-tocotrienol inhibited NF-κB activity and the expression of NF-κB regulated gene products. They note that inflammatory transcription factor NF-κB is involved in tumorigenesis, so inhibition of NF-κB may be how tocotrienols exert their anti-cancer effects.

These preclinical results are promising and show that:

“δ-tocotrienol is the most bioactive tocotrienol against human pancreatic cancer cells and provide the rationale for selecting δ-tocotrienol as the lead tocotrienol compound for further studies of the use of tocotrienols for pancreatic cancer prevention and treatment.”

A phase I clinical trial is ongoing (NCT00985777) evaluating the use of δ-tocotrienol in patients with pancreatic tumors.

While Vitamin E supplementation may yet be of benefit to healthy individuals, it could have benefit in patients with pancreatic cancer, so it will be interesting to see how this develops.

ResearchBlogging.orgHusain, K., Francois, R., Yamauchi, T., Perez, M., Sebti, S., & Malafa, M. (2011). Vitamin E  -Tocotrienol Augments the Anti-tumor Activity of Gemcitabine and Suppresses Constitutive NF- B Activation in Pancreatic Cancer Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-11-0424

Academic institutions are now bringing pharma/biotech companies together and facilitating rational combination trials that make solid scientific sense.

Combining at least two targeted drugs looks to be increasingly necessary in order to develop innovative new cancer treatments, where turning off one target may stimulate another, thus both need to be targeted for there to be an overall effect.

However, one company may not have all the pathways and drug targets covered by their portfolio.  The result is that companies may have to work together in combination trials with each providing one drug from their portfolio.

That was one of the key messages I took from Gordan Mills (UT MD Anderson Cancer Center) in his recent video interview with Sally Church from Pharma Strategy Blog:

Sally Church’s video interview with Professor Mills is well worth watching if you have not already done so.

Not only are universities and research institutions well placed to judge the scientific merits, but as Mills points out they can facilitate things as an independent third party and actively help bring partnerships together.  Given that combination therapies may be needed in order to turn off different parts of signaling pathways and cross-talk, I think we are likely to see more of this approach.

It’s going to be new territory for many companies – how to enter into a potential joint venture or alliance? However, if it results in a therapy that works, it is going to be win-win for all parties. It may also improve efficiency in drug development and lead to better use of patients in early stage development.

Some examples of where this is happening already in oncology include AstraZeneca and Merck with their MEK-AKT approach and GSK (MEK) with Novartis (PI3K), to name a couple.  This is a new trend we are likely to see more of in the future.

I can see universities hiring alliance managers who have industry experience to ensure these collaborations run smoothly.

The topic of the industry/academia interface in rational cancer drug development will also be discussed in a plenary session at the forthcoming American Association for Cancer Research (AACR) meeting on Molecular Targets and Cancer Therapeutics (November 12-16, 2011) in San Francisco.

How academia can better help the pharma/biotech industry bring innovative, rational drug combinations to market is a topic that I think we will be reading more about in coming months.

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