Fig. 2

The dynamics of distinct tumor cell populations upon systemic therapy. Many tumors respond well to the initial therapy; although the existence of intratumoral cellular heterogeneity is widely acknowledged, it is generally believed that the evolution of treatment-resistant clones requires additional genetic events and usually takes at least several months (left). Our data indicate that even short-term (neoadjuvant) exposure of BRCA1-driven tumors to platinum therapy results in the replacement of tumor mass by BRCA1-proficient cells [29]. While cells with BRCA1 LOH die almost immediately after beginning of the treatment, clones with retained BRCA1 continue to proliferate during platinum exposure and rapidly repopulate the tumor lump (right)