Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Abstract

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.

The methods of in vitro selection of chemotherapeutic druds for individual chemotherapy of maligant tumors in patinets

“…Уменьшение АТФ указывает на лекарственную чувствительность, а отсутствие снижения -на устойчивость к химиопрепаратам. Этот анализ пригоден для измерения выживаемости культур с низкой плотностью клеток [47,48,49,50,51,52]. Используя данный тест, корейские ученые оценили in vitro чувствительность к гемцитабину первичных культур клеток рака поджелудочной железы и обнаружили достоверную корреляцию между химиочувствительностью и возникновением раннего рецидива у 57 пациентов после хирургической резекции и адъювантной химиотерапии.…”

“…Одни авторы показали преимущества методов индивидуального определения химиочувствительности перед стандартной химиотерапией, и, опираясь на высокую корреляцию ответов на культурах клеток с клиническими (реакция опухолей, состояние пациентов, протяженность периодов безрецидивной и общей выживаемости), высказались в поддержку развития методов [16,25,47,50]. Другие исследователи не смогли выявить преимуществ методов инди-видуальной оценки химиочувствительности перед протокольными, и заняли отрицательную позицию [19,49,51,82,130]. Третьи ученые выявили лишь частичные преимущества в персонифицированном тестировании восприимчивости неопластических клеток к химиопрепаратам и заняли промежуточную позицию [25,49].…”

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

“…The grouping of the patients into drug resistance profiles is also unclear and may have been a result of an otherwise small sample size . The CTR‐Test also uses this technology and in a small study with patient‐derived tissue from glioma tumors found a good fit of resistance as measured in the test with clinical resistance in 11 patients …”

“…The grouping of the patients into drug resistance profiles is also unclear and may have been a result of an otherwise small sample size [155]. The CTR-Test also uses this technology and in a small study with patient-derived tissue from glioma tumors found a good fit of resistance as measured in the test with clinical resistance in 11 patients [156] In contrast to the EDR, the Adenosine triphosphate (ATP) readout method measures luminescence of intra-cellular ATP as a surrogate marker for drug sensitivity. Assays using this readout method make up a large proportion of publications studying chemoresponse assays.…”

“…Other studies without a randomization procedure using glioma, ovarian, and breast patient‐derived cells in 2D significant association with clinical factors such as grading, tumor stage, tumor subtype, and Ki67 were found. In these studies no comparison was made with patient clinical outcome parameters . Using a 3D spheroid technology combined with an ATP readout, the SpheroNEO Study found significant differences between breast cancer patients with pathologic complete response and those with residual tumor following neoadjuvant chemotherapy .…”