Radiation Oncology/Radiobiology/Cancer Stem Cell

Cancer Stem Cell

• First identified by John Dick in acute myeloid leukemia in the late 1990s
• Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample
• CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types

Warburg hypothesis

• Warburg theory of cancer postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria
• The term Warburg effect in oncology describes the observation that cancer cells, and many cells grown in vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire
• Observation that cancer cells exhibit glycolysis with lactate production and mitochondrial respiration even in the presence of oxygen
• IDH mutation
  • Sue Han et al. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020 May;122(11):1580-1589. (PMID: 32291392)
  • Jiangjiang Li et al. Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer. Theranostics. 2018; 8(15): 4050–4061. (PMID: 30128035)

Telomere Shortening

• Cagatay Gunes et al. Telomeres in cancer. Differentiation. 2018 Jan-Feb;99:41-50. (PMID: 29291448)
• Hueng-Chuen Fan et al. Telomeres and Cancer. Life (Basel). 2021 Dec 16;11(12):1405. (PMID: 34947936)

Microsatellite Instability

• Hiroyuki Yamamoto et al. Microsatellite instability: an update. Arch Toxicol. 2015 Jun;89(6):899-921. (PMID: 25701956)
• Kai Li et al. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020 Jan 13;20:16. (PMID: 31956294)

Multidrug resistance (MDR, PMID: 19949920)

• MDR refers to a phenomenon that the cancer cells develop resistance to a variety of structurally unrelated anticancer drugs, which is the leading cause of treatment failure in cancer
• Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc.