title: Protecting the normal in order to better kill the cancer.
abstract: Chemotherapy is the only option for oncologists when a cancer has widely spread to different body sites. However, almost all currently available chemotherapeutic drugs will eventually encounter resistance after their initial positive effect, mainly because cancer cells develop genetic alterations, collectively coined herein as mutations, to adapt to the therapy. Some patients may still respond to a second chemo drug, but few cases respond to a third one. Since it takes time for cancer cells to develop new mutations and then select those life-sustaining ones via clonal expansion, "run against time for mutations to emerge" should be a crucial principle for treatment of those currently incurable cancers. Since cancer cells constantly change to adapt to the therapy whereas normal cells are stable, it may be a better strategy to shift our focus from killing cancer cells per se to protecting normal cells from chemotherapeutic toxicity. This new strategy requires the development of new drugs that are nongenotoxic and can quickly, in just hours or days, kill cancer cells without leaving the still-alive cells with time to develop mutations, and that should have their toxicities confined to only one or few organs, so that specific protections can be developed and applied.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota, 55912.
authors.forename: Lewis
authors.initials: L
authors.lastname: Ezeogu
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota, 55912.
authors.forename: Lucas
authors.initials: L
authors.lastname: Zellmer
authors.affiliation: Beijing Baofa Cancer Hospital, Shahe Wangzhuang Gong Ye Yuan, Chang Pin Qu, Beijing, 102206, China.
authors.forename: Baofa
authors.initials: B
authors.lastname: Yu
authors.affiliation: Laboratory of Cell and Molecular Biology, Cancer Institute, Chinese Academy of Medical Science, Beijing, 100021, China.
authors.forename: Ningzhi
authors.initials: N
authors.lastname: Xu
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota, 55912.
authors.forename: Dezhong
authors.initials: D
authors.lastname: Joshua Liao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Chemoresistance; Chemotherapy; Metastasis; Mutation