Differentiation
How closely a cancer cell still resembles the mature, specialised tissue it came from. Well-differentiated tumours look like their parent tissue and tend to behave better; poorly differentiated ones look primitive and grow faster.
Normal cells mature from stem cells into specialised types with fixed jobs; cancer partly reverses this, and the degree of reversal is a core component of tumour grade. Differentiation also determines which markers a tumour carries and which drugs reach it: a prostate cancer that dedifferentiates into a neuroendocrine form stops making PSA and stops responding to hormone therapy, and EGFR-mutant lung cancers can escape osimertinib by transforming into small-cell histology. A few drugs work by forcing differentiation, most famously all-trans retinoic acid, which makes the immature cells of acute promyelocytic leukaemia mature and die.
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