HER2 Support Group Forums - View Single Post - any tumor tests to predict which chemos work better?

gdpawel · 02-13-2012, 08:16 AM

Her2, PTEN, PI13K, and all genes, are under the direct regulation and control of genetic elements that no one has ever studied. Two percent of the human genome that codes for known proteins (the part that everyone currently studies) represents only 1.20th of the whole story. One of the most important cancer related genes (PTEN) is under the regulation of 250 separate, unrelated genes. Drug selection would still be a guessing game, which a lot of empirical treatment is today.

While (apoptotic) cell death is of importance in hematologic (non-solid) cancers (easy to do with blood), like many leukemias and lymphomas, it does not represent cancer cell death in all circumstances and can be an unreliable parameter in many solid tumors. Labs that measure only one mechanism of cell death miss important cell responses that are critical to accurate prediction of clinical response.

While apoptosis represents an important mechanism of programmed cell death, it is only one of several cell death pathways. Apoptotic cell death occurs with certain mutational events, DNA damage, oxidative stress and withdrawal of some growth factors particularly within the immune system. Non-apoptotic programmed cell death includes: programmed necrosis, para-apoptosis, autophagic cell death, nutrient withdrawal, and subtypes associated with mis-folden protein response, and PARP mediated cell death.

Yes. The tumor needs to be live "fresh" to have "traditional" chemo-sensitivity testing. When it comes to drug selection, investigators can only measure those analytes (substance or chemical constituent) in paraffin wax that they know to measure. If you are not aware of and capable of measuring a biologically relevant event, you cannot seek to detect it. The cell-lines in paraffin-embedded tissue can change over time. These proliferating populations of cell are biologically distinct in their behavior from "fresh" live cells that comprise human tumors.

The functional platform (that Rational Therapeutics and Weisenthal Cancer Group) uses morphologic (structure) and metabolic (cell metabolism) endpoints (point of termination) to gauge cellular response to drugs in human tumor microspheroids (microclusters) isolated from surgical biopsies/specimens. By examining drug-induced cell death events in native-state microclusters, the functional profiling platform has the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction. The microclusters recapitulate the human tumor environment.

Newer forms of assays are being provided by private U.S. companies such as Precision Therapeutics (ChemoFx and BioSpeciFx assays), Rational Therapeutics (EVA-PCD and TARxGET assays), DiaTech Oncology (the MiCK "microculture kinetic" assay), and the Weisenthal Cancer Group (CytoRx, EGFRx and AngioRx assays).

Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy. Patients benefit both in terms of response and survival from drugs and drug combinations found to be "active" in assays even after treatment failure with several other drugs, many of which are in the same class, and even with combinations of drugs found to have low or no activity as single agents but which are found in the assay to produce a synergistic and not merely an additive anti-tumor effect.

There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic therapy. Only your tumor specimen goes to the lab, not the patient.

The choice of a lab is not a geographical consideration, but a technical consideration. All of the labs are experienced and capable of providing very useful information.

However, the labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. Some labs have been offering these assays as a non-investigational, paid service to cancer patients, in a situation where up to 30 different drugs and combinations are tested, at two drug concentrations in three different assay systems.

The labs will provide you and your physician with in depth information and research on the testing they provide. Absent the assays, the oncologist will perform "trial-and-error" treatment until he/she finds the right chemotherapy regimen. You should have the right chemo in the first-line of treatment.

By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to your own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.

The two labs that provide the functional profiling platform are Rational Therapeutics and Weisenthal Cancer Group.

http://www.rationaltherapeutics.com/Contact-Us.aspx
http://www.rationaltherapeutics.com/...andidates.aspx

http://weisenthalcancer.com/Contact_Us.html
http://weisenthalcancer.com/Specimens.html

Best wishes!

02-13-2012, 08:16 AM	#7
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	Re: any tumor tests to predict which chemos work better? Her2, PTEN, PI13K, and all genes, are under the direct regulation and control of genetic elements that no one has ever studied. Two percent of the human genome that codes for known proteins (the part that everyone currently studies) represents only 1.20th of the whole story. One of the most important cancer related genes (PTEN) is under the regulation of 250 separate, unrelated genes. Drug selection would still be a guessing game, which a lot of empirical treatment is today. While (apoptotic) cell death is of importance in hematologic (non-solid) cancers (easy to do with blood), like many leukemias and lymphomas, it does not represent cancer cell death in all circumstances and can be an unreliable parameter in many solid tumors. Labs that measure only one mechanism of cell death miss important cell responses that are critical to accurate prediction of clinical response. While apoptosis represents an important mechanism of programmed cell death, it is only one of several cell death pathways. Apoptotic cell death occurs with certain mutational events, DNA damage, oxidative stress and withdrawal of some growth factors particularly within the immune system. Non-apoptotic programmed cell death includes: programmed necrosis, para-apoptosis, autophagic cell death, nutrient withdrawal, and subtypes associated with mis-folden protein response, and PARP mediated cell death. Yes. The tumor needs to be live "fresh" to have "traditional" chemo-sensitivity testing. When it comes to drug selection, investigators can only measure those analytes (substance or chemical constituent) in paraffin wax that they know to measure. If you are not aware of and capable of measuring a biologically relevant event, you cannot seek to detect it. The cell-lines in paraffin-embedded tissue can change over time. These proliferating populations of cell are biologically distinct in their behavior from "fresh" live cells that comprise human tumors. The functional platform (that Rational Therapeutics and Weisenthal Cancer Group) uses morphologic (structure) and metabolic (cell metabolism) endpoints (point of termination) to gauge cellular response to drugs in human tumor microspheroids (microclusters) isolated from surgical biopsies/specimens. By examining drug-induced cell death events in native-state microclusters, the functional profiling platform has the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction. The microclusters recapitulate the human tumor environment. Newer forms of assays are being provided by private U.S. companies such as Precision Therapeutics (ChemoFx and BioSpeciFx assays), Rational Therapeutics (EVA-PCD and TARxGET assays), DiaTech Oncology (the MiCK "microculture kinetic" assay), and the Weisenthal Cancer Group (CytoRx, EGFRx and AngioRx assays). Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy. Patients benefit both in terms of response and survival from drugs and drug combinations found to be "active" in assays even after treatment failure with several other drugs, many of which are in the same class, and even with combinations of drugs found to have low or no activity as single agents but which are found in the assay to produce a synergistic and not merely an additive anti-tumor effect. There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic therapy. Only your tumor specimen goes to the lab, not the patient. The choice of a lab is not a geographical consideration, but a technical consideration. All of the labs are experienced and capable of providing very useful information. However, the labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. Some labs have been offering these assays as a non-investigational, paid service to cancer patients, in a situation where up to 30 different drugs and combinations are tested, at two drug concentrations in three different assay systems. The labs will provide you and your physician with in depth information and research on the testing they provide. Absent the assays, the oncologist will perform "trial-and-error" treatment until he/she finds the right chemotherapy regimen. You should have the right chemo in the first-line of treatment. By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to your own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered. The two labs that provide the functional profiling platform are Rational Therapeutics and Weisenthal Cancer Group. http://www.rationaltherapeutics.com/Contact-Us.aspx http://www.rationaltherapeutics.com/...andidates.aspx http://weisenthalcancer.com/Contact_Us.html http://weisenthalcancer.com/Specimens.html Best wishes!