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2018 | 16 | 2 | 96–100
Article title

Komórki macierzyste raka jako tarcza dla terapii celowanej

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Cancer stem cells in targeted therapy
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Cancer stem cells (CSCs) are one of the causes of failure in the treatment of patients with malignant tumors. Although these cells account for only about 2% of the tumor mass, they possess unique properties, such as self-renewal, unlimited proliferation, asymmetric cell division and the ability to form dormant cells. Cancer stem cells are responsible for treatment failure as they are resistant to standard anticancer treatment (chemo- and radiotherapy), leading to cancer progression, metastases and relapse. They carry specific biomarkers which enable their identification and isolation. The most common markers identified in breast, ovarian, and endometrial cancer as well as in other localizations include: CD44+, C117 (c-Kit), CD133+ (promin), ALDH1 (aldehyde dehydrogenase 1), Oct-4 (POU5F1), nestin and BMI1. Cancer stem cells take advantage of numerous signaling pathways (Wnt, SHH – sonic hedgehog homologue, PI3K/AKT/mTOR). Studies have demonstrated that clinical advantage can be gained using salinomycin (an antibiotic isolated from Streptomyces albus), or metformin, an antidiabetic drug. Research is continued on targeted therapy aimed at cancer stem cells: both cancer stem cell biomarkers or signaling pathways (their components) used by cancer stem cells may be targeted. Studies on microRNA, which coordinates the expression of multiple genes, and on metabolic strategies targeting cellular mitochondria are underway.
Jedną z przyczyn niepowodzeń leczenia chorych na nowotwory złośliwe jest istnienie komórek macierzystych raka (cancer stem cells, CSCs). Stanowią one tylko 2% masy guza, ale mają unikalne właściwości, takie jak samoodnawianie, nieograniczona proliferacja, niesymetryczne podziały i przebywanie w stanie utajenia (dormant cells). Komórki macierzyste raka są oporne na standardowe leczenie (chemio- i radioterapię), powodują więc progresję raka, przerzutowanie i nawroty. Mają swoiste biomarkery, na których podstawie identyfikuje się je oraz izoluje. Do najczęściej wykrywanych markerów w raku piersi, jajnika, endometrium, a także w innych lokalizacjach narządowych należą: CD44+, C117 (c-Kit), CD133+ (promina), ALDH1 (dehydrogenaza aldehydowa 1), Oct-4 (POU5F1), nestyna i BMI1. Komórki macierzyste raka korzystają z licznych szlaków sygnałowania (Wnt, SHH – sonic hedgehog homologue, PI3K/AKT/mTOR). Badania wykazały, że można uzyskać kliniczną korzyść, stosując salinomycynę (antybiotyk wyizolowany ze Streptomyces albus) albo lek przeciwcukrzycowy – metforminę. Trwają badania nad terapią celowaną: tarczą mogą być zarówno biomarkery komórek macierzystych raka, jak i szlaki sygnałowania (lub ich składowe), z których one korzystają. W centrum zainteresowania są również mikroRNA, koordynujące ekspresję wielu genów, i strategie metaboliczne celowane na mitochondria komórkowe.
Physical description
  • Katedra i Klinika Onkologii, Oddział Ginekologii Onkologicznej, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Poznań, Polska
  • Klinika Ginekologii Onkologicznej, Centrum Onkologii – Instytut im. Marii Skłodowskiej-Curie, Oddział w Krakowie, Kraków, Polska
  • Swedish Orphan Biovitrum, Warszawa, Polska
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