Targeting genomic instability in cancer
Summary
Genomic instability is a defining feature of cancer, which arises when the cellular systems that maintain DNA integrity falter, enabling the accumulation of genetic and epigenetic alterations that drive malignant transformation. It is both the architect of cancer's evolution and its Achilles' heel. Targeting genomic instability has reshaped oncology: first through systemic chemotherapy and external beam radiation and then with poly(ADP-ribose) polymerase (PARP) inhibitors in homologous rec
Content
# Targeting genomic instability in cancer
*Published: 2026 Apr 16*
Genomic instability is a defining feature of cancer, which arises when the
cellular systems that maintain DNA integrity falter, enabling the accumulation
of genetic and epigenetic alterations that drive malignant transformation. It is
both the architect of cancer's evolution and its Achilles' heel. Targeting
genomic instability has reshaped oncology: first through systemic chemotherapy
and external beam radiation and then with poly(ADP-ribose) polymerase (PARP)
inhibitors in homologous recombination repair-deficient tumors and other DNA
damage response targets. Recently, tumor-targeted DNA-damaging platforms, namely
antibody-drug conjugates (ADCs) and radiopharmaceuticals, have emerged alongside
modern precision medicine strategies to optimize patient selection, develop
rational combinations, and widen the therapeutic index.
DOI: 10.1016/j.cell.2026.03.035