for gdpawel and others interested in chemosensitivity assays to predict effectiveness

[Lani]

of treatments according to her2 status, etc

J Int Med Res. 2007 Nov-Dec;35(6):753-61. Links
Correlation Between the In Vitro ATP-based Chemosensitivity Assay and HER2/neu Expression in Women with Breast Cancer.

Woo SU, Bae JW, Kim HG, Choi SH, Kang DH, Lee JB, Koo BW.
Department of Surgery, Korea University College of Medicine, Seoul, Korea.
Several in vitro chemosensitivity tests have been developed to predict the chemotherapeutic response of tumours prior to initiation of individualized treatment for breast cancer. This study investigated whether the in vitro chemosensitivity response of cell lines derived from breast cancer patients was affected by HER2/neu expression. We cultured breast cancer cell lines from 50 patients and the adenosine triphosphatebased chemotherapy response assay (ATPCRA) was performed with 5-fluorouracil, gemcitabine, docetaxel, doxorubicin, methotrexate, vinorelbine and paclitaxel. 5-Fluorouracil combined a high median cell death rate (32.4%) with the narrowest range of cytotoxic effects (7.3 - 65.7%). In addition, gemcitabine showed significantly greater activity in HER2/neupositive patients. In contrast, docetaxel was significantly less effective in HER2/neu-positive patients. No significant correlation was found between the other agents and HER2/neu expression. The use of the ATP-CRA test for metastatic tissue from patients with recurrent disease might be a useful approach to determine the most effective chemotherapy regimen.
PMID: 18034988 [PubMed - in process]

[SoCalGal]

Hi Lani,
I know that Joe asked us to post links, but for a lay person like me and many others, it's more helpful to read when you paraphrase and add lay-woman's terms.

Am checking out all of your postings this week - still trying to figure out what to do next - if anything.
Thanks Flori

[gdpawel]

The ATP assay is one of three non proprietary assays. The others are the DISC and MTT (Oncologic In Vitro Chemoresponse Assays). All three are known as "cell-death" assays. Assays based on "cell-death" occur in the entire population of tumor cells, as opposed to only in a small fraction of the tumor cells occuring in "cell-growth" assays.

The one technique that stands out about the above study is the fact that they investigated whether the in vitro chemosensitivity response of "cell lines" derived from breast cancer patients (they cultured breast cancer "cell lines"). Cell-lines have proved worthless as models to predict the activity of drugs in cancer. An "established" cell-line is not reflective of the behavior of fresh "live" tumor cells in primary culture in the lab, much less in the patient. They have been a huge disappointment with respect to their ability to correctly model the disease-specific activity of new drugs for any cancers, much less in breast cancer.

It is important to culture "live" solid tumor specimens in conical polypropylene (a slippery material) which encourages tumor cells to remain in the form of three dimensional, floating clusters (their natural state). This increases the proportion of tumor cells relative to normal cells.

And selecting for tumor cells is very important for an assay like the ATP, which cannot discriminate between tumor cells and normal cells. It is chiefly used in situations where there are very pure population of tumor cells, but a very low cell yield. There are certain assay culture methods, like the DISC assay, that can get rid of the non-cancer cells before the end of the culture period. It would be more beneficial to utilize two or all three of the mentioned assays.

Dr. Ian Cree, with Queen Alexandra Hospital's Translational Oncology Research Centre in the UK, performed the first ever prospective, randomized clinical trial of physician's choice chemotherapy verus ATP assay-directed chemotherapy in non-surgically debulked, platinum-resistant ovarian cancer. He presented it at the May, 2005 ASCO meeting in Orlando, Florida. The results were highly suggestive of an effect due to the assay and the most successful drug regimens used were nearly all developed using the assay.

Cree's lastest research uses his ATP-based cell culture assay to assess the expression of genes in dozens of fresh NSCLC tumor samples. Gene expression markers can actually be calibrated to provide information about chemo resistance and sensitivity.

Cree IA, Kurbacher CM, Lamont A, et al. A prospective randomized controlled trial of ATP-based tumor chemosensitivity assay-directed chemotherapy versus physicians choice in patients with recurrent platinum-resistant ovarian ancer. BMC Cancer. 2003; 3:19.