CISTAX · Discovery of molecular markers for the inverse relationship between platinum and taxane resistance in cancer
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2008-10-01 → 2010-09-30
- Финансиране от ЕС
- 185 736 €
- Участници
- 1
- Схема
- MC-IIF
Линиите свързват координатора с партньорите.
Накратко на български
Молекулярни маркери определят защо някои ракови клетки, станали устойчиви на цисплатин, стават по-чувствителни към паклитаксел. Това ще помогне да се установи кои пациенти биха имали полза от редуване на тези два вида химиотерапия.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Discovery of molecular markers for the inverse relationship between platinum and taxane resistance in cancer
An EACR travel fellowship allowed me to spend a week at the laboratory of my collaborators Dr. Jean-Pierre Gillet and Prof. Michael Gottesman at the National Cancer Institute (NCI). My research investigates patterns of resistance and sensitivity in cancer cell lines to two chemoterapy drugs, cisplatin and paclitaxel. When cisplatin resistance is developed in the laboratory 68% of cells lines are not resistant to paclitaxel and some even become more sensitive to paclitaxel. The reverse is also true of paclitaxel-resistant cell lines. 66% showed no resistance to cisplatin or were more sensitive to cisplatin. This research suggests that two-thirds of cancer patients would benefit from receiving chemotherapy which alternates between cisplatin and paclitaxel, because developing resistance to one could make their cancer more sensitive to other drug. The challenge for me is how to identify which patients will respond to alternating therapy between cisplatin and paclitaxel. While two-thirds of cancer patients may respond well to this treatment strategy, the other third would respond poorly and need to be treated differently. Through collaboration with the Gottesman lab and several other groups I have put together a panel of drug-resistant cell lines which either have the inverse resistance phenotype between cisplatin and paclitaxel or are cross resistant to both drugs. I will be looking for "molecular markers": genes and proteins which correspond with the inverse resistance pattern. I will determine wheter these molecular markers change in the same way in samples from ovarian cancer patients. Once validated in clinical samples, these molecular markers could be used as a clinical test to determine if an individual patient is likely to respond to cisplatin or paclitaxel and therefore model the smaller group of patients who are cross-resistant to both agents. We took a targeted approach to examining gene expression by performing profiling with a custom TLDA array designed by the Gottesman group. This assays the expression of 380 genes previously associated with drug resistance and response to chemoterapy. Gene families examined included; ABC transporters, DNA repair genes, apostosis-associated genes, glutathione metabolism, copper metabolism and many others.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Abstract Aim: To identify a gene and protein expression pattern associated with platinum resistance and taxane sensitivity in a panel of drug-resistant cancer cell lines. Background: Despite the success of early detection programs and surgical techniques for the treatment of cancer many patients will still require chemotherapy. Initial responsiveness to chemotherapy is high, however the majority of patients ultimately relapse with resistant disease. This research proposal will examine resistance to two commonly used classes of chemotherapy, platinums and taxanes. When cancer cells become resistant to platinum chemotherapy they often become sensitive to taxanes and vice versa. This inverse relationship happens in all cancer types and the mechanism of this relationship is not understood. Research Project: This project will study gene and protein expression in a large panel of drug resistant cell lines in an attempt to understand the mechanism of the inverse resistance relationship between platinums and taxanes. This process will discover a set of molecular markers predicting the inverse relationship between platinum and taxanes. These have the potential to be translated to the clinic and be used to identify patients likely to respond to platinum or taxane chemotherapy. Outcomes: The success of research projects like the one described in this application have the potential to revolutionise cancer therapy by individually tailoring chemotherapy. This will significantly increase the response rate of both platinum and taxane chemotherapy as it will allow the identification of patients likely to respond to treatment. Patients identified as being resistant to both agents could then be treated with alternative chemotherapy. The understanding of the mechanism of the inverse resistance relationship may also reveal new targets for cancer therapy.
Оригинален текст от CORDIS (на английски).
Участници
- DUBLIN CITY UNIVERSITY · DublinКоординаторИрландия
Връзки
Данни: CORDIS, © Европейски съюз