Cancer stem cells markers in ovarian cancer: Clinical and therapeutic significance (Review)

Królewska-Daszczyńska, Patrycja; Wendlocha, Dominika; Smycz‐Kubańska, Marta; Stępień, Sebastian; Mielczarek‐Palacz, Aleksandra

doi:10.3892/ol.2022.13585

Cited by 7 publications

(6 citation statements)

References 89 publications

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“…Olaparib has been FDA-approved for the treatment of germline BRCA -mutated (g BRCA m), HER2 − BC and g BRCA m ovarian cancer (Mandapati & Lukong, 2023; Singh, Parveen, & Yadav, 2021), and Buparlisib and similar PI3K inhibitors are in clinical trials for use in BC and ovarian cancer, with Alpelisib approved for use in PIK3CA -mutated BCs. (Yu et al, 2023) As ovarian cancers are also linked to germline and somatic BRCA1 mutations (Berchuck et al, 1998; Stratton et al, 1997), and are thought to harbor CSCs like BC (Cioffi et al, 2015; Krolewska-Daszczynska, Wendlocha, Smycz-Kubanska, Stepien, & Mielczarek-Palacz, 2022), this combination of drugs may prove effective beyond the BC context. Following this logic, combined Olaparib and Alpelisib has shown promise in a Phase 1b clinical trial in breast and ovarian cancers (Konstantinopoulos et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence

Petrella,

Chen,

Ravelo

et al. 2024

Preprint

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Cancer stem-like cells (CSCs) are posited to exhibit specialized oncogenic capacity to drive malignancies. CSCs are distinguished by enhanced hallmarks of cancer, including apoptosis avoidance, phenotypic plasticity and aberrant growth pathway signaling. Standard-of-care chemotherapies targeted to rapidly cycling cells routinely fail to eliminate this resistant subpopulation, leading to disease recurrence and metastasis. Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, is enriched for tumor-propagating CD44+/CD24-/low> CSCs, which are poorly ablated by chemotherapeutics and are associated with poor prognosis. CD44 governs sustained PI3K signaling in breast cancer, which is essential for CSC maintenance. PI3K inhibition can elicit DNA damage and down-regulate BRCA1 expression, which in turn enhance the synthetic lethality of PARP inhibitors. Here, we examined a dual chemotherapeutic approach targeting these pathways by combining a pan-PI3K inhibitor (Buparlisib) and a PARP1 inhibitor (Olaparib) on a panel of TNBC cell lines with distinct mutational profiles and proportions of CSCs. We observed differential sensitivity to this dual inhibition strategy and varying cellular stress and resistance responses across eight TNBC lines. The dual chemotherapeutic effect is associated with a reduction in S-phase cells, an increased in apoptotic cells and elevated expression of cleaved PARP, indicating a provoked replicative stress response. We observed that PARP/PI3K inhibition efficacy was potentiated by repeated administration in some TNBC lines and identified critical treatment schedules, which further potentiated the dual chemotherapeutic effect. Dual inhibition induced small but significant increases in CSC relative abundance as marked by CD44+/CD24-/low or ALDH1+ cells and increased stress and survival signaling in multiple TNBC cell lines, suggesting this sub-population contributes to TNBC chemoresistance. These results suggest the additive effects of PARP and PI3K inhibition against CSC phenotypes may be enhanced by temporally-staged administration in TNBC cells.

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Section: Discussionmentioning

confidence: 99%

Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence

Petrella,

Chen,

Ravelo

et al. 2024

Preprint

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“…The acquisition of oncogenic genetic and epigenetic alterations determines aggressiveness, invasiveness, and treatment resistance [ 48 , 49 ]. Cancer cells may gain stemness due to an oncogenic hit [ 50 ].…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

“…Some markers expressed on the surface of CSCs correlate with clinical features and can potentially be used for the diagnosis of, and the prediction of prognosis in, ovarian cancer [ 131 ]. The presence of these specific markers can be used to identify CSCs in ovarian cancer [ 49 ].…”

Section: Ovarian Cancer Stem Cells Markersmentioning

confidence: 99%

“…CD133, a pentaspan transmembrane glycoprotein, is a well-known marker of CSCs and has been identified in various cancers [ 49 ]. Although the biological function of CD133 remains unknown, it has been suggested to participate in primitive cell differentiation and epithelial–mesenchymal interactions, autophagy, and, thus, in the malignant progression of ovarian cancer [ 132 ].…”

Section: Ovarian Cancer Stem Cells Markersmentioning

confidence: 99%

“…CD24 is a mucin-type adhesion molecule localised in lipid rafts via its glycosylphosphatidylinositol anchor [ 49 ]. Human CD24 is located on chromosome 6q21 [ 193 ].…”

Section: Ovarian Cancer Stem Cells Markersmentioning

confidence: 99%

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The Role of Cancer Stem Cell Markers in Ovarian Cancer

Frąszczak,

Barczyński

2023

Cancers

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Ovarian cancer is the most lethal gynaecological cancer and the eighth most common female cancer. The early diagnosis of ovarian cancer remains a clinical problem despite the significant development of technology. Nearly 70% of patients with ovarian cancer are diagnosed with stages III–IV metastatic disease. Reliable diagnostic and prognostic biomarkers are currently lacking. Ovarian cancer recurrence and resistance to chemotherapy pose vital problems and translate into poor outcomes. Cancer stem cells appear to be responsible for tumour recurrence resulting from chemotherapeutic resistance. These cells are also crucial for tumour initiation due to the ability to self-renew, differentiate, avoid immune destruction, and promote inflammation and angiogenesis. Studies have confirmed an association between CSC occurrence and resistance to chemotherapy, subsequent metastases, and cancer relapses. Therefore, the elimination of CSCs appears important for overcoming drug resistance and improving prognoses. This review focuses on the expression of selected ovarian CSC markers, including CD133, CD44, CD24, CD117, and aldehyde dehydrogenase 1, which show potential prognostic significance. Some markers expressed on the surface of CSCs correlate with clinical features and can be used for the diagnosis and prognosis of ovarian cancer. However, due to the heterogeneity and plasticity of CSCs, the determination of specific CSC phenotypes is difficult.

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