Is Lapatinib (Tykerb) a P13K inhibitor?

[jojo]

My question is shown above in subject title box, thanks!

[Cathya]

JoJo;

I don't believe so. The following article mentions a couple of P13K inhibitors that are currently either in clinical trials or being developed....and lets hope quickly!

Cathy

Lack of response to trastuzumab for breast cancer may reverse if PI3K inhibitor added

Cancer Weekly - May. 01, 2006 2006 MAY 1 - (NewsRx.com) -- Breast cancer patients with HER2-positive tumors who don't respond to Herceptin (trastuzumab) may benefit from cocktail therapy that includes Herceptin along with one or more PI3K inhibiting agents, according to researchers at The University of Texas M. D. Anderson Cancer Center.

Their findings, reported at the annual meeting of the American Association for Cancer Research (AACR), were made in cell culture and mice studies, but are so promising that a phase 1/2 clinical trial will start at M. D. Anderson in HER2-positive breast cancer patients whose disease has progressed despite Herceptin treatment. Herceptin is Genetech's formulation of the monoclonal antibody trastuzumab.

"More than half of patients with HER2-positive tumors don't respond to Herceptin as a single agent, and our research has shown us why that is and what might be done to help these patients," said lead author Dihua Yu, MD, PhD, professor in the Department of Surgical Oncology.

Combining PI3K inhibitors with existing therapies also might provide additional benefit in treating other breast tumor types.

In 2004, Yu and her research team reported that patients who don't respond to Herceptin have very low levels of PTEN in their breast tumors, whereas women who respond have higher levels of this protein. In normal cells, PTEN is a powerful tumor suppressor gene that helps control cell division. In about half of all of breast tumors ( HER2-positive or not), however, PTEN levels are very low or the protein is completely missing.

It was known that when Herceptin, a monoclonal antibody, binds to the HER-2 protein on the outside of tumor cells it takes days for the protein to degrade. But Yu found that within 10 minutes of administration, Herceptin activated PTEN. This suggested that Herceptin works by rapidly mobilizing PTEN in addition to inhibiting HER-2 growth signals, she said.

PTEN is known to block the effect of a growth-promoting protein known as PI3K, which itself controls an oncogenic pathway that includes the cell proliferation kinases Akt and mTOR.

In this study, the research group tested seven different PI3K inhibitors that are either used or under development for clinical trials. They found that one, RAD001 (everolimus), had better antitumor activity when combined with Herceptin than did Herceptin or RAD001 alone.

Another PI3K inhibitor, TCN-P (triciribine), showed significant benefit when used in combination with Herceptin, Yu says. Even with a low dose of TCN-P, the combination therapy halted growth of PTEN-deficient HER2-positive breast tumors implanted in mice.

Based on preclinical data from Yu's team, Francisco Esteva, MD, PhD, an associate professor in the Department of Breast Medical Oncology, will be conducting the clinical trial.

[Becky]

If you had a low mitotic (Ki67) score that implies a slow to divide cancer, do you think that your PTEN levels would be normal or low/non-existant?


Thanks in advance

Becky

[jojo]

Didn't somebody just mention about having her PTEN levels tested? If such a test does exist, I would like to know, thanks.

[Barbara2]

Becky, I would like to know the answer to your question as well.


Before starting late herceptin, I asked my onc if I should have the PTEN testing done. He didn't advise it. His rationalle was "Even if you had a low PTEN score, wouldn't you still want herceptin in case it would benefit you? So why spend the money on the test?"

Barbara

[RobinP]

Hi Jojo and All,

I discussed pTEN extensively in prior postings. Look it up in the search button. Also, see Targeted Molecular Diagnostics for pTEN testing.

By the way Lapatinib blocks her2 and her1; in such it may downstream pi3k but it is not a specific pi3k inhibitor.

Hope this helps,
Robin

[Becky]

At this point, I am not going to get the Pten test only because I will finish my year of Herceptin in mid June (although my onc wants to continue until September which covers my first 2 yrs since diagnosis and keeps me on the Herceptin/Arimidex combo for one full year).


I thought about testing my tumor (because I could rationalize - why stay on longer than the year if I don't have Pten. Also, I would worry more than maybe I would even need to. What I mean by that is that, prior to adjuvant Herceptin, most Her2+ women did okay and did not recur. So...)

I was just wondering if anyone found research that correlates other indicators to each other.

Also, does anyone diffinitively know if you test positive for a hormone receptor - is positive positive. What I mean is that my PR is "less than 5%" on my pathology report. I have read alot about this type of reading and some research says anything under 5% is negative and other research says that anything positive is positive.

Those of you who are ER/PR negative - did your pathology reports actually say negative?

I am hoping my PR - less than 5% is at least a bit positive. My onc - who is good says its something but would be considered negative if push came to shove.

Best regards

Becky