Model of tumor dormancy/recurrence after short-term chemotherapy.
Although many tumors regress in response to neoadjuvant chemotherapy, residual tumor cells are detected in most cancer patients post-treatment. These residual tumor cells are thought to remain dormant for years before resuming growth, resulting in tumor recurrence. Considering that recurrent tumors are most often responsible for patient mortality, there exists an urgent need to study signaling pathways that drive tumor dormancy/recurrence. We have developed an in vitro model of tumor dormancy/recurrence. Short-term exposure of tumor cells (breast or prostate) to chemotherapy at clinically relevant doses enriches for a dormant tumor cell population. Several days after removing chemotherapy, dormant tumor cells regain proliferative ability and establish colonies, resembling tumor recurrence. Tumor cells from "recurrent" colonies exhibit increased chemotherapy resistance, similar to the therapy resistance of recurrent tumors in cancer patients. Previous studies using long-term chemotherapy selection models identified acquired mutations that drive tumor resistance. In contrast, our short term chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that can resume growth after drug removal. Studying unique signaling pathways in dormant tumor cells enriched by short-term chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Shenduo
S
Li
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Margaret
M
Kennedy
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Sturgis
S
Payne
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Kelly
K
Kennedy
Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
Victoria L
VL
Seewaldt
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Salvatore V
SV
Pizzo
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Robin E
RE
Bachelder
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors
D000970:Antineoplastic Agents