The increasing appreciation of the importance of autophagy as consequence of
cancer therapy or underlying disease biology is illustrated by the large number of papers that are evaluating autophagy as a
cancer target. While autophagy is often linked to the generation of metabolic precursors, it is also important in diseases where
protein production is a hallmark of the disease itself, such as
pancreatic cancer and
multiple myeloma.
Multiple myeloma is characterized by ongoing autophagy as a consequence of constitutive
immunoglobulin production, which creates the need for efficient transfer and disposal of misfolded or unfolded
proteins. In order to survive this cellular stress, plasma cells depend on proteasomal degradation of the large volume of misfolded
proteins as well as the autophagy pathway. It has previously been suggested that the excess
proteins not targeted to the
proteasome, or that accumulate when the
proteasome is inhibited through the use of chemically active agents such as
bortezomib, are linked to impaired cell survival, and that their packaging in the form of an aggresome somehow minimizes their 'proteotoxicity' allowing these toxic
proteins to be sequestered away from normal cellular machinery.