CD44 and colorectal cancer: Mechanistically, inhibition of HIF-2α effectively attenuates the stemness phenotypes through inactivating the PI3K/AKT/CD44 pathway.926 Acidosis, a hallmark of the tumor microenvironment, acts as a promoting factor for the stemness phenotype in melanoma, prostate cancer, colorectal cancer, and gastric cancer.927 The extracellular acidic microenvironment may become another promising target for the treatment of CSCs.