EGFR Positive UPSC and Clear Cell Patients

lindaprocopio said:

I am so sorry that something I posted long ago haunts you now.
I hate to see someone who was feeling hopeful read something that shakes their faith in the wisdom of that hope. Knowledge is power, but not if it haunts you in the darkest part of the night. (((Pat))) I was really focused on EGRF when I was first diagnosed in 2008 with UPSC (stage 3-c) since it scared me because it is so prevalent in papillary serous cancers. In fact I SAVED an article all this time, plus some notes from Greg ("gdpawel" is the handle I think he posts under here), which is now somewhat dated (2007), on that subject. I want to paste it in here, because it does offer treatment suggestions for those with EGFR and there is HOPE when there are targeted treatments to try. You might want to post on the Ovarian Cancer Board here and ask for those women's experiences with PARP1 inhibitors, which look promising for EGFR.

Here you go:

Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden, April 18, 2007, concluded that "functional profiling" with cell culture assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity of Iressa, Tarceva, Sutent, Nexavar, and Avastin in primary cultures of "fresh" human tumors).

Cell Culture Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.

Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.

There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell culture assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

"Functional profiling" measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, "functional profiling" is measuring them through the surrogate of measuring if the cell is alive or dead.

For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.

The "functional profiling" technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.

This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Author/Speaker/Performer :Larry Weisenthal, M.D., Ph.D.; Contact information: phone: (714) 596-2100.

The 102 page pdf on this is still available at this Link: http://weisenthal.org/Weisenthal_ESCIa.pdf Source : Eur J Clin Invest 37 (suppl. 1):60, 2007


and here's something more from the Komen Fdn:
Cetuximab. Triple-negative tumors are known to overexpress EGFR,[20] and 2 studies presented at SABCS 2007 explored the role of cetuximab, a humanized monoclonal antibody directed against EGFR, in this tumor type. Both of the trials included a platinum agent because preclinical data suggested that triple-negative tumors may have defects in BRCA1-mediated DNA repair and thus may be sensitive to DNA-damaging agents such as platinums.[21]

An ongoing study in metastatic triple-negative breast cancer is evaluating the role of sunitinib antiangiogenesis monotherapy compared with best available chemotherapy.[27] Other emerging targets for treatment incorporate components of cellular proliferative pathways, including the phosphoinositide 3-OH kinase pathway and the mitogen-activated protein kinase pathway, DNA repair, and growth-factor receptors such as EGFR and c-kit. Agents currently in phase 1/2 evaluation for triple-negative disease include dasatinib and PARP1 inhibitors. It is hoped that further advances in targeted treatment and optimization of chemotherapy will provide more effective treatment and improved outcomes for this aggressive subclass of breast cancer.

Gracegoi said:

Hi Pat
I had to look EGFR up and did find an artical that said it could be valuable in future research .

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745284/

I did not have the finances to have mine tested outside of the standard of care. I believe I asked if it was tested and if it could be. I don't remember the answer. That was over two years ago.

It has taken me a while to trust doctors that they are doing the best job. In hindsight , I put my oncologist through alot .

Grace