*3.3. Peroxisomal ABC Transporters and Cancer*

Beyond its recognized role in metabolism and redox homeostasis, the peroxisome is now increasingly regarded as a signaling platform and a key organelle in cellular metabolic reprogramming with major consequences on the immune response, cell cycle, and cell differentiation [12,96]. Elegantly presented in the state of the art of Hlaváˇc and Souˇcek, several studies have revealed a significant association between the level of expression of peroxisomal ABC transporters and various cancers [97]. This suggests a role of these ABC transporters in cell cycle control, cell differentiation, and tumorigenesis. Downregulation of peroxisomal ABC transporters has been observed in several cases: *ABCD1* in

melanoma [98] and renal cell carcinoma [99], *ABCD2* in breast cancer [100], and *ABCD3* in ovarian cancer [101] and colorectal cancer [102]. Moreover, a lower prognostic value has been associated with low expression of *ABCD1* in ovarian cancer [103] and low expression of *ABCD3* in colorectal cancer [102]. On the contrary, *ABCD1* and *ABCD3* were found upregulated in breast carcinoma [104], and a positive correlation was observed between *ABCD3* expression and glioma tumor grades [105]. Recently, VLCFA accumulation was associated with colorectal cancer [106]. Increased endogenous elongation appears to be primarily responsible for this observation, but peroxisomal ABC transporters are also likely involved, and the ability to regulate their expression could potentially represent a therapeutic interest in such cancers. Altogether, further studies are required to understand the link between the transport function and metabolic role of peroxisomal ABC transporters and the control of cell cycle with regard to the complexity of tumor heterogeneity.
