Tuesday, January 22, 2008

Chemo! Finally!

After three weeks of delays because of my chest infection, I was finally able to start a new chemo combination today: Taxol + Tykerb.

I had Taxol before, but with two other drugs. This Taxol/Tykerb combination is new, so there are no studies that compare this with the usual Taxol/Xeloda combination. In fact, the FDA (U.S. Federal Drug Adminstration) approval for Tykerb was only in combination with Xeloda. It hasn't been tested with other drugs, inluding the Taxol I'm getting. So again, I'm a bit of a guinea pig with this one.

Tomorrow, I'm going to talk to a research clinic here about a clinical trial. All I know about it so far is that it's only for Stage IV metastatic breast cancer patients. In other words, patients on their last legs who don't mind having untested drugs because they don't have much of a chance otherwise. But I figure, if I die, at least I can contribute something toward research that will help other women after me. I just have to make sure I'm helpful, rather than just a sacrifice.


Anonymous said...

Dear Shin,

I am sorry to hear about your breast cancer and good luck with your Tykerb combination therapy. You might be interested to know of the study reported at the San Antonio Breast Cancer symposium which indicates that Tykerb might target cancer stem cells, which are believed to drive metastasis.

Good Luck.

Background: Previously, we have shown that tumorigenic breast cancer cells (CD44+/CD24-/low) were resistant to conventional chemotherapy. Residual cancers showed an increase in tumorigenic CD44+/CD24-/low cells, enhanced tumor-initiation by mammosphere (MS) formation, and increased new tumor formation by xenograft transplantation assays. Molecular pathways like EGFR/HER2 have been shown to be aberrant in CSCs. Methods: We performed a neoadjuvant clinical trial in 30 patients with locally advanced HER-2 overexpressing breast cancers who received lapatinib (EGFR/HER2 tyrosine kinase inhibitor) given initially as a single agent for the first 6 weeks, followed by a combination of weekly trastuzumab and 3-weekly docetaxel for 12 weeks before primary surgery. Pathologic response in the surgical specimens after neoadjuvant therapy was assessed. Sequential core biopsies of the primary cancers were taken in patients at time of diagnosis and after week 6 of lapatinib, and assessed for tumorigenic CD44+/CD24-/low cells by flow cytometry, and MS formation. Global gene expression differences between cancer cells bearing CD44+/CD24-/low cells and all other sorted cells, and between cancer MS and the primary bulk invasive cancers were analyzed. Results Significant tumor regression in the product of bidimensional tumor measurements with a median decrease of 60.8% (range 0, -86.5%, p=0.001) was observed in primary tumors after only 6 weeks of single agent lapatinib. Unlike with chemotherapy, lapatinib treatment decreased tumorigenic CD44+/CD24-/low breast cancer cells from 10.6% to 4.7%, and also reduced self-renewal capacity measured by MS assays (30 to 15 MS/10,000 cells, p=0.01). The pathologic complete response rate after lapatinib and trastuzumab/docetaxel was much higher than expected, at 63%(16/25). The gene transcription pathways that underlie chemoresistant, MS-forming CD44+/CD24-/low cells involve genes belonging to stem cell self-renewal, Notch (Jagged-2, Hes1, Lunatic fringe, mastermind-like 2), Hedghog (Cyclin B1, CDC2), and Wnt pathways, FOXP1, growth factor/PI3K/AKT signaling (AKT3, BCL2, CTNNB1, FGFR2, FOXO1A, FOXO3A, PIK3R1, PTEN), and early development pathways (JARID2, JMJD2C, and MBNL1), regardless of HER2 expression in the primary tumor. Conclusion Contrary to conventional chemotherapy, human breast cancer specimens obtained from this prospective in vivo study has demonstrated for the first time, that lapatinib decreases tumorigenic breast cancer stem cells in the primary breast cancers of women receiving neoadjuvant treatment. This data suggests that specific signaling inhibitors of the pathways responsible for stem cell self-renewal could provide a therapeutic strategy for eliminating tumorigenic cells in order to achieve long-term eradication of cancer.

Shin said...


Thanks for your comment and for the abstract from the Tykerb study. I've been reading that there's a lot of cancer research looking at stem cells. I wish they'd hurry up! By the way, John is a fairly common name, so I don't know which John you are. Would you mind telling me your last name? And how you come to know so much about Tykerb studies? I could learn a lot from you.



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