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- W1499702189 abstract "PL04-03 Drug resistance remains a major obstacle to prolonging the lives of cancer patients. Recently, investigators have become more aware of the influence of the tumor microenvironment on tumor cell survival and growth. Hematological malignancies serve as a model for studying tumor-microenvironment interactions using the bone marrow as the primary microenvironment factor. The central hypothesis is that the bone marrow microenvironment provides a sanctuary for subpopulations of malignant cells to evade or circumvent drug-induced death and that this represents a form of de novo drug resistance. We use the term “environment-mediated drug resistance or EMDR” to describe the combination of mechanisms that contribute to this form of de novo drug resistance. By definition, de novo drug resistance is associated with conditions that protect cells from initial drug exposure and therefore are present during drug selection. EMDR includes a combination of soluble factors and cell contact, and can be subdivided into soluble factors - mediated drug resistance, and cell adhesion mediated drug resistance. We propose that the tumor microenvironment protects tumor cells from drug-induced stress and cell death by two primary mechanisms: (a) a paracrine mechanism due to soluble cytokine and/or growth factors produced as a result of the tumor cell: environment interaction, and (b) a physical contact mechanism referred to as “cell adhesion-mediated drug resistance,” (CAM-DR). This protection allows tumor cells to survive the insult of chemotherapy, leading to minimal residual disease (MRD), and thereby increases the probability for the development of acquired drug resistance. Targeting the microevironment for new drug discovery provides a unique approach to improving treatment outcomes for hematological malignancies, and possibly other cancers. Interrupting tumor cell: bone marrow microenvironment interaction and/or signal transduction mechanisms associated with these interactions represents a novel approach to enhancing treatment effect and improving patient outcomes." @default.
- W1499702189 created "2016-06-24" @default.
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- W1499702189 date "2008-08-01" @default.
- W1499702189 modified "2023-09-26" @default.
- W1499702189 title "The influence of the tumor microenvironment on drug response and drug resistance" @default.
- W1499702189 hasPublicationYear "2008" @default.
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