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[Cross and non-cross resistant anticancer agents to multidrug-resistant cultured cells from hematologic malignancies]
M Shimoyama1, Y Ishida, T Ohtsu
1Hematology-Oncology and Clinical Cancer Chemotherapy Division, National Cancer Center Hospital.
Abstract:
We report here that typical and atypical multidrug resistant (MDR) cells can be identified by monoclonal antibodies, MRK16 and MRK20, respectively. Typical MDR cells were cross-resistant to vinca alkaloids, anthracyclines, mitoxantrone (MXT), etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK16. Atypical MDR cells were cross-resistant to anthracyclines, MXT, VP-16, and bleomycin but sensitive to vinca alkaloids and ACT-D. They were reactive to MRK20, but not to MRK16. Among anthracyclines, aclacinomycin A was not cross-resistant to either typical or atypical MDR cells. Methotrexate was not cross-resistant to doxorubicin, vincristine, Ara-C and cisplatin. Cisplatin was not cross resistant to 5-FU, either. Identification of cross and non-cross resistant anticancer agents may be useful to plan a cure-oriented combination chemotherapy for hematologic malignancies.
Insights
Monoclonal antibodies MRK16 and MRK20 can identify typical and atypical multidrug resistant (MDR) cells. This discovery aids in selecting effective combination chemotherapy for hematologic malignancies.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Context:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- Identifying distinct MDR phenotypes is crucial for treatment optimization.
Purpose:
- To characterize typical and atypical multidrug resistant (MDR) cells using monoclonal antibodies MRK16 and MRK20.
- To investigate the cross-resistance patterns of these MDR cell types to various anticancer agents.
Summary:
- Typical MDR cells, recognized by MRK16, exhibit cross-resistance to vinca alkaloids, anthracyclines, mitoxantrone (MXT), etoposide (VP-16), and actinomycin-D (ACT-D).
- Atypical MDR cells, identified by MRK20, are cross-resistant to anthracyclines, MXT, VP-16, and bleomycin, but sensitive to vinca alkaloids and ACT-D.
- Specific agents like aclacinomycin A, methotrexate, and cisplatin show unique non-cross-resistance patterns, offering potential therapeutic avenues.
Impact:
- This research provides a method for distinguishing MDR cell types, enabling more precise treatment strategies.
- Understanding differential drug resistance can guide the development of targeted combination chemotherapy regimens for hematologic malignancies.
- The findings may improve cure rates and reduce treatment failure in patients with hematologic cancers.