ABCB1 is one of the major drug efflux transporters that is known to cause multidrug resistance (MDR) in cancer patients receiving chemotherapy for the treatment of solid tumors and hematological malignancies.
Cryptophycins are highly promising drug candidates, as their biological activity is not negatively affected by P-glycoprotein, a drug efflux system commonly found in multidrug-resistant cancer cell lines and solid tumors.
Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies.
Using Pgp and MRP as molecular markers to detect MDR tumor cells is technically demanding, and solid tumors in particular contain heterogeneous cell populations.
These cell lines represent a model of a solid tumor in which overexpression of Pgp, a combination of increased Pgp and decreased topoII alpha, and a decrease of topoII alpha are represented.
In this article, the authors examine the literature and summarize the various techniques used to measure MDR1 gene expression, patterns of expression in adult solid tumors.
We investigated the feasibility and sensitivity of a method for probing Pgp-mediated drug transport in cells isolated from solid tumors, using xenograft models.
Preliminary studies demonstrated the presence of P-gp in tumor samples from patients with acute leukemia, multiple myeloma, lymphomas, and a variety of solid tumors.