Cancer Stem Cell Biomarkers Predictive of Radiotherapy Response in Rectal Cancer: A Systematic Review

Abstract

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitourinary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradication of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients.

The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer

“…CD44 expression in cancer has been correlated with both poor and favourable outcomes [49]; however, growing evidence now suggests that overexpression of CD44 and its isoforms is an unfavourable prognostic indicator in cancer patients [50][51][52][53][54][55][56][57][58][59][60][61]. A list of some of these studies, although not comprehensive, is provided in Table 1.…”

Stemness, Inflammation and Epithelial–Mesenchymal Transition in Colorectal Carcinoma: The Intricate Network

“…In animal experiments, CD44-positive malignant cells show the classic features of TICs. As few as 100 CD44 + cells are sufficient to initiate tumour formation in nude mice [ 33 ]. In cancers, CD44 is associated with clonality, metastatic spreading ability, resistance to chemotherapy and lower overall survival [ 24 , 33 , 34 , 35 ].…”

“…As few as 100 CD44 + cells are sufficient to initiate tumour formation in nude mice [ 33 ]. In cancers, CD44 is associated with clonality, metastatic spreading ability, resistance to chemotherapy and lower overall survival [ 24 , 33 , 34 , 35 ]. Regarding the resistance to treatment, patient-derived organoid analysis has shown an association between the resistance of organoids to 5-fluorouracil and high CD44 expression in carcinomas of the upper gastrointestinal tract [ 36 ].…”

Challenges in precision medicine in pancreatic cancer: A focus in cancer stem cells and microbiota

“…These niches maintain the principal properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system and facilitate their metastatic potential (8)(9)(10). Interestingly, biomarkers related to CSCs and its niche/TME have been found to be among the most accurate in prediction of disease progression and, specially, disease recurrence (11)(12)(13) and also to develop tailored therapies that optimize patient's opportunities to cure (14) A variety of tumors contain bacteria what suggests that the microbiome could play a role in the TME (15). In fact, the microbiome is proposed to have an active involvement in the pathogenesis and treatment responses.…”

“…These niches maintain the principal properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system and facilitate their metastatic potential ( 8 – 10 ). Interestingly, biomarkers related to CSCs and its niche/TME have been found to be among the most accurate in prediction of disease progression and, specially, disease recurrence ( 11 – 13 ) and also to develop tailored therapies that optimize patient’s opportunities to cure ( 14 )…”