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20.20: Cáncer resistente al tratamiento

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Molecular Biology

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Treatment Resistant Cancers

20.20: Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or impaired apoptosis.

Origin of resistant cells

Given the heterogeneous nature of the cancer cells, a tumor can have various cancer cell subpopulations, each with distinct genetic fingerprints. Some of these cells may have pre-existing mutations or acquire new mutations that confer them drug resistance. Under therapeutic pressure, cancer cells obey the Darwinian law of evolution, and only the cells that are most adaptive and resistant to treatment survive and multiply to take over other susceptible cancer cell subpopulations.

Models for cancer resistance

Two models are put forward to explain resistance to anticancer drugs. One is the cancer stem cells (CSC) model, and another is the Environment-mediated drug resistance (EMDR) model.

Cancer stem cells or CSCs are quiescent cells with increased DNA repair efficiency, altered cell cycle parameters, or overexpression of anti-apoptotic properties or drug transporters. In this model, drug resistance is mostly caused by the intrinsic or acquired resistance of accumulating CSCs and not all cancer cells within a tumor.

In the Environment-mediated drug resistance (EMDR) model, cancer cells interact with the surrounding environment to enter a quiescent or dormant state to escape the drugs. Inside their protective zone composed of the tumor microenvironment, cancer cells undergo genetic changes until they acquire resistant phenotype. The cells can then relapse once the drug is withdrawn.

Lectura sugerida


Treatment Resistant Cancers Cancer Cell Mutation Immune Escape Rapid Drug Resistance Alteration In Drug Transport Modification Of Drug Target DNA Damage Response Impaired Apoptosis Cancer Cell Subpopulations Pre-existing Mutations Acquired Mutations Darwinian Law Of Evolution Cancer Stem Cells Model Environment-mediated Drug Resistance Model

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