Alopecia represents a multifaceted challenge with distinct etiologies and consequences. Transposed to the world of oncology, different types of alopecia and molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. In patients with cancer, alopecia can be iatrogenic (i.e., due to conventional chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy and surgery) or a direct consequence of the disease itself (e.g., malnutrition, scalp metastases and paraneoplastic syndromes). Identification of the actual incriminated mechanism(s) is therefore essential in order to deliver appropriate supportive care, whether preventive or curative. On the preventive side, the last few years have seen the advent of the automated cooling cap, a prophylactic approach supported by several randomized clinical trials. On the curative side, although the treatments currently available are limited, several promising therapeutic approaches are under development. Appropriate alopecia management is essential, particularly regarding its psychological repercussions with significant consequences on the quality of life of patients and their family and with a potential impact on treatment compliance.
Colorectal cancer (CRC) initiation and progression result from the accumulation of genetic and epigenetic alterations. Although aberrant gene expression and DNA methylation profiles are considered hallmarks of CRC development, the precise timing at which these are produced during tumor establishment remains elusive. Here we investigated the early transcriptional and epigenetic changes induced by Apc inactivation in intestinal crypts. Hyper-activation of the Wnt pathway via Apc inactivation in crypt base columnar (CBC) intestinal stem cells (ISC) led to their rapid accumulation driven by an impaired molecular commitment to differentiation, which was associated with discrete alterations in DNA methylation. Importantly, inhibiting the enzymes responsible for de novo DNA methylation restored the responsiveness of Apcdeficient intestinal organoids to stimuli regulating the proliferation-to-differentiation transition in ISC. This work reveals that early DNA methylation changes play critical roles in the establishment of the impaired fate decision program consecutive to Apc lossof-function.Significance : This study demonstrates the functional impact of changes in DNA methylation to determine the colorectal cancer cell phenotype following loss of Apc function.
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