Interestingly, caspase-independent apoptosis physiologically occurs with higher frequency than previously noticed, often as an anticancer defense: notably, caspase-3-negative cell death occurs in anti-tumor instances such as spontaneous (Kitanaka et al., 2002) or immune-mediated (Ren et al., 2012) tumor regression, or EGF-induced differentiation (Fombonne et al., 2004). Here, EGF is linked to neoplasm.