Drug resistance continues to be a
major barrier to the delivery of curative therapies in cancer. Historically,
drug resistance has been associated with over-expression of drug transporters,
changes in drug kinetics or amplification of drug targets. However, the
emergence of resistance in patients treated with new-targeted therapies has
provided new insight into the complexities underlying cancer drug resistance.
Recent data now implicate intratumoural heterogeneity as a major driver of drug
resistance. Single cell sequencing studies that identified multiple genetically
distinct variants within human tumours clearly demonstrate the heterogeneous
nature of human tumours. The major contributors to intratumoural heterogeneity
are (i) genetic variation, (ii) stochastic processes, (iii) the
microenvironment and (iv) cell and tissue plasticity. Each of these factors
impacts on drug sensitivity. To deliver curative therapies to patients,
modification of current therapeutic strategies to include methods that estimate
intratumoural heterogeneity and plasticity will be essential.
Source: Role of intratumoural heterogeneity
in cancer drug resistance: molecular and clinical perspectives. Saunders NA,
Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, Minchin RF, Guminski
A. EMBO Mol Med. 2012 Aug;4(8):675-84.
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