Under pressure: clonal hematopoiesis in patients receiving cancer therapy

In clonal hematopoiesis (CH), hematopoietic stem cells (HSCs) with mutations conferring a fitness advantage preferentially expand under evolutionary constraints. Over the last decade, cancer therapy has emerged as a selective pressure contributing to high rates of CH in patients with hematological and nonhematological cancers. Distinct chemotherapies, radiotherapies, immunotherapies, and targeted cancer therapies shape somatic evolution by inducing de novo mutations and by conferring a selective advantage to pre-existing CH clones. Such expansion may influence treatment response and toxicity, and is linked to the development of therapy-related myeloid neoplasms. CH prevalence will continue to increase as treatment options expand, cancers are detected earlier, and patients live longer. Managing CH and its adverse effects has the potential to improve cancer outcomes and survivorship.