The “Hallmarks of Cancer” paper by Douglas Hanahan and Robert Weinberg is a classic, and a must read (allow plenty of time) for anyone interested in cancer drug development.
The original 2000 paper, updated in 2011, identified six hallmarks of cancer, “distinctive and complementary capabilities that enable tumour growth and metastatic dissemination:”
- Sustaining Proliferative Signaling
- Evading Growth Suppressors
- Activating Invasion and Metastasis
- Enabling Replicative Immortality
- Inducing Angiogenesis
- Resisting Cell Death
Apoptosis or programmed cell death according to Hanahan and Weinberg is “a natural barrier to cancer development.” One of the ways cancer cells survive is by resisting cell death and disrupting the apoptosis signaling pathway; in other words the normal signals that trigger cell death don’t get through.
Researchers have shown that apoptosis is controlled at the cellular level, in the mitochondrion, by the Bcl-2 family of regulatory proteins (BCL-2, BCL-XL). Targeting BCL-2 (a protein that prevents apoptosis) could induce cell death and be a potentially successful anti-cancer strategy.
The result of our increased understanding of cancer biology has been the development of novel targeted drugs such as ABT-199, a potent and selective BCL-2 inhibitor. This is in early clinical development by AbbVie ($ABBV), a new biopharmaceutical company spun off from Abbott Laboratores ($ABT) last week.
I’m not a great fan of Twitter lists, especially those that imply you are a “Top Cat,” because they can end up being divisive and generate resentment in those not included.
That said, without wishing to offend anyone, here’s my initial starting point of those I will be following at the 2012 annual meeting of the American Society of Hematology in Atlanta from December 8 – 11 (#ASH12):
American Society of Hematology
Companies /Industry Execs
Physicians/Researchers & Institutions
This is not intended to be a definitive list, so I encourage you to watch the #ASH12 Twitter stream for additional people to follow depending on your interests. I have intentionally not included PR folks, investors, journalists who are usually too busy writing their own stuff and exhibitors who just want to tweet their own news. However, if I have missed anyone who has a burning desire to be included, please contact me.
Wifi permitting (always a big IF since many conference venues have not invested sufficiently in infrastructure to cope with demand) I’m hoping there will be a good Twitter conversation in Atlanta.
One of the hot topics this year is Multiple Myeloma, for which there are four “Super Friday” satellite symposia and over 700+ abstracts.
Earlier this year, the FDA approved Onyx’s carfilzomib (Kyprolis) and approval for Celgene’s pomalidomide (Actimid) is expected by year-end. Several other new agents are on the horizon including Millennium’s new proteasome inhibitor ixazomib/MLN9708 that Dr Sundar Jagannath discussed at the recent Chemotherapy Foundation Symposium in New York. The availability of new treatment options is certainly good news for patients.
I am looking forward to attending the ASH education session on Keeping Pace with Advances in Myeloma. Hope to see you there if you have plans to be in Atlanta next week.
New treatments for multiple myeloma (MM) are changing the treatment landscape and that is set to continue over the next few years as several new products come to market.
This year we have seen the FDA approval of subcutaneous bortezomib (Velcade®) and carfilzomib (Kyprolis®). Approval for pomalidomide is anticipated soon.
Earlier this week at the 2012 Chemotherapy Foundation Symposium in New York, Sundar Jagannath, M.D., Professor of Medicine at Mt. Sinai School of Medicine presented on “New IMiD and Proteasome Inhibitors.”
Dr Jagannath told a large audience at the Symposium (also known as the Greenspan Meeting) that he hoped “pomalidomide will get accelerated approval and be in your hands by New Year”.
In his presentation, Jagannath discussed some of the new products in development. One that he mentioned in detail was MLN9708/ixazomib (Millennium), a new reversible, oral proteasome inhibitor currently in early clinical trials.
He noted that is not just being developed as a single agent in advanced disease, but is already being tested in combination with lenalidomide and dexamethasone therapy in earlier settings.
Companies with MM drugs in the pipeline will need to look closely as to how the treatment landscape may change in the next few years if new products such as ixazomib are approved and replace existing products such as bortezomib.
Although Dr Jagannath’s talk was very informative from a new product development perspective, I did wonder whether some of the community medical oncologists in the audience, who only see a few myeloma patients, might have benefitted from a more practice orientated perspective.
I sat next to a community oncologist from Florida, for example, who told me he found the MM treatment regimens difficult to understand for the few patients that he saw.
Dr Jagannath concluded his presentation with the thought that “rapid strides in genomics promises new drugs and personalized medicine in the near future.”
I look forward to hearing more about the latest research in Multiple Myeloma at the annual meeting of the American Society of Hematology (ASH 2012) in Atlanta next month.