CES1 and cancer: Previous studies have shown that targeting lipolysis or FAO can sensitize tumors to chemotherapy, radiotherapy, and anti-angiogenetic treatment, thus providing a rationale for combining CES1 inhibitors with standard of care agents.6 Notwithstanding this potential for synthetic lethality, the effective management of high-risk groups of CRC patients may require rational drug combinations built on an improved stratification of CMS4 (and CMS2) tumors that target synergistic cancer-cell co-vulnerabilities.