Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘cancer oncology’

2008 – a strange year in the world of oncology

By on December 21, 2008

Inspired by Paulo Nuin, I thought it would be a good idea for the last post of the year before the Christmas holidays to be a list; the good, the bad and the ugly.


Best of the best

FriendFeed’s Life Scientists Room

Best Purchase

HBA and SCIP Memberships

Worst Purchase

Buying a 2 GB flash drive and then picking up 2 free ones at ASCO a week later, doh!

Best New Technology

Discovering the Cloud – who needs desktop apps?

Best software

Evernote Premium Upgrade – it's a great web 2.0 database for storing snippets and clips of data

Worst Software

MS Office for Mac – it garbled scientific symbols in large files

Best blog/site

Discovering WordPress.org

Worst Blog/Site

Best left unsaid

Best Scientific Meeting

AACR

Worst Scientific Meeting

ASH – usually my favourite, but this year it got too big and too full of non-cancer topics

Best Cancer Data

Triple and quadruple induction therapy with Vel/Rev/Dex/Pred led to 100% response rates and survival not yet defined after 8 months.  Some patients were still in remission after 2 years.

Best Non-Cancer data by an oncology drug

Gleevec (imatinib) may be effective in Type I diabetes.

Worst Cancer Data

Any drug that fails is a disappointment, as are yet more 'me-too-not-very-effective' chemotherapies such as toiposomerase inhibitors.

Best new cancer drug in development

Abiraterone from Cougar Biotech


What categories would you have for your list?  Do tell.






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Has there been any real progress in treatment

By on December 10, 2008

In the battle for survival in solid tumors ince Larry Einhorn reported that chemotherapy could cure testicular cancer?
That was the question my primary care doctor asked me today during a visit to review a back injury. After reviewing the evidence, we both reluctantly agreed that all progress since then in solid tumors such as breast, lung, colorectal etc was largely incremental.

In liquid tumors such as leukemia and lymphoma, however, the picture is much rosier with the advent of Rituxan and Gleevec for the treatment of NHL and CML respectively, as well as improvements in bone marrow transplantation (SCT). SCT is curative in some patients, but must be balanced by a 20% risk of mortality from the procedure itself.

For all the interesting developments with targeted therapies, our knowledge of the science and biology still has a long way to go before we can start using the big C word, cure.

Cancer-initiating cells and tumor resistance

By on June 30, 2008

A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. The chromosome that is labeled with green and red spots (up left) is the one where the wrong rearrangement is present

Positive metaphase Bcr-Abl in CML highlighted by FISH

Recent discoveries about the role of stem cells in cancer have created new opportunities for cancer research. As scientists learn more of their cancer-initiating properties, stem cells are emerging as potential therapeutic targets for many types of cancers.

The existence of a small population of 'cancer-initiating cells'
responsible for tumour maintenance was originally demonstrated in
leukemia and the concept is also being tested in a variety of solid tumours. 

Leukemia-initiating cells, particularly those that are in the quiescent
state, are thought to be resistant to both chemotherapy and targeted
therapies, resulting in disease relapse.  Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the
leukemia-initiating cell pool may not always be eradicated by current therapy,
leading to disease relapse on drug discontinuation.  Although relapse in CML is rare (<10-15% of cases), when it does occur the stem cells can replicate in significant numbers. 

More recently, the role of promyelocytic leukemia protein (PML) tumour
suppressor in hematopoietic stem cell maintenance has been examined.  A new
therapeutic approach for targeting quiescent leukemia-initiating cells
and possibly cancer-initiating cells by pharmacological inhibition of
PML may evolve.

Similarly, the role of quiescent stem cells in breast cancer has been reported, with small studies involving the targeted small molecule kinase inhibitor, lapatinib.  Other studies have noted a relationship between stem cells and patient outcomes in pancreatic, bladder, breast and glioma carcinomas, for example. 

Present chemotherapy options eliminate the bulk of the tumour but leave a core of these cancer stem cells with high capacity for repair and renewal.  Identifying the stem cells and designing new therapies is therefore a key focus in drug development for the near future.

Sources:

Nature

Leukemia

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PI3-Kinase in cancer and tumorigenesis

By on June 10, 2008

Image via Wikipedia

The chemical signaling pathways that control the life cycle of cells offer many important targets for cancer researchers hoping to stop the growth of tumours, yet the complex nature of these pathways may make it virtually impossible to kill a cell with a single therapeutic bullet.

Mutations in genes that encode components of the phosphoinositide 3-kinase (PI3K) pathway are one of the most frequent events observed in solid tumours.  The PI3K pathway can be activated by overproduction of growth factors, chemokines or mutations in growth factor factor receptors such as Ras, PTEN or P3IK itself.  Activation of the PI3-kinase pathway has been linked to a diverse group of cellular functions, including cell growth, proliferation, differentiation, motility and survival, all important aspects of tumourigenesis.

Genetic studies in mice reveal that the insulin-like growth factor (IGF), PI3K and Akt pathway provides a synergistic signal for Hedgehog tumour formation. Interestingly, there is a high incidence of loss-of-function mutations of PTEN, a negative regulator of PI3-kinase activity, in approx. 39% of Hedgehog-dependent human pancreatic cancers. 
Researchers have looked at inhibition of PI3-kinase in a study of breast cancer cells.  Their findings suggest that molecules used to inhibit the MEK protein, similar to those being studied to control breast cancer growth, can "switch on" another pathway that keeps cancer cells from dying.

At the recent ASCO meeting in Chicago, a number of papers were presented looking at prognostic factors, proteomic analysis and various inhibitors in early phase clinical trials, including XL765 from Exelixis, temsirolimus from Wyeth, NVP-BEZ235 and SF1126.  It is too early to tell if the pathway is critical to the tumour's survival, but time will tell.

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New life for old cancer drug? Will Iressa bounce back in breast cancer?

By on June 5, 2008

Epidermal growth factor receptor

Image via Wikipedia

Iressa (gefitinib), a EGFR inhibitor, originally received fast track approval from the U.S. Food &
Drug Administration for non-small cell lung cancer (NSCLC) in 2003 amid much brouhaha.  Two years later, AstraZeneca (AZN)
were forced to stop marketing the drug in the U.S. because it failed in the phase III clinical trial to extend patients lives and improve survival.

Doctors continued to research the drug, however, which is how doctors at M.D. Anderson Cancer Center in Houston made the interesting discovery that Iressa can significantly delay the spread of
breast cancer when given along with standard hormone therapy.  The results were reported at the 2008 annual ASCO meeting.

The idea behind the study was that preclinical data provide evidence that suggests crosstalk between
growth factor receptor pathways and the estrogen receptor (ER). 
Inhibition of both epidermal growth factor receptor and ER signalling
may therefore be a potential intervention to overcome hormonal resistance.

A total of 94 women with newly diagnosed hormone sensitive (ER+) metastatic breast cancer (mBC) were randomized to receive Arimidex (anastrozole) 1
mg/day and either gefitinib 250 mg/day or placebo. The goal was to measure progression-free survival (PFS) in the phase II setting. 

The results were interesting – Arimidex plus Iressa was well tolerated and associated with a
marked advantage in PFS compared with Arimidex plus placebo.  Further trials may be forthcoming to determine if the combined inhibition of both epidermal growth factor receptor and ER signalling will extend lives in postmenopausal
women with newly diagnosed hormone sensitive mBC.

{UPDATE: the 2009 ASCO meeting starts tomorrow and it will be interesting to see what new data will be coming out on both Iressa and also other EGFR inhibitors.}

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