title: Intratumoral functional heterogeneity and chemotherapy.
abstract: Intratumoral heterogeneity including genetic and nongenetic mechanisms refers to biological differences amongst malignant cells originated within the same tumor. Both, cell differentiation hierarchy and stochasticity in gene expression and signaling pathways may result in phenotypic differences of cancer cells. Since a tumor consists of cancer cell clones that display distinct behaviours, changes in clonal proliferative behavior may also contribute to the phenotypic variability of tumor cells. There is a need to reveal molecular actions driving chemotherapeutic resistance in colon cancer cells. In general, it is widely hypothesized that therapeutic resistance in colorectal cancer is a consequence of the preferential survival of cancer stem cells. However, recent data regarding colorectal cancer suggest that resistance to anticancer therapy and post-therapeutic tumor reappearence could be related to variations of clonal dynamics. Understanding the interaction of genetic and nongenetic determinants influencing the functional diversity and therapy response of tumors should be a future direction for cancer research.
authors.affiliation: Ferenc Sipos, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.affiliation: Ferenc Sipos, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Constantinovits
authors.affiliation: Ferenc Sipos, Miklós Constantinovits, Györgyi Műzes, 2 Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy; Clonal dynamics; Colorectal cancer; Functional heterogeneity; Oxaliplatin; Xenograft