Non-oncogene addiction of multiple myeloma to the autophagy adapter p62


Year: 2016

Number: 3/4


Non-oncogene addiction of multiple myeloma to the autophagy adapter p62

Owing to deregulated growth, cancer cells experience more stress than normal counterparts, and thus are highly dependent on adaptive stress responses. Such non-oncogene addiction offers targets with previously unpredicted therapeutic specificity (1).
Paradigmatic is multiple myeloma (MM, ~2% of all cancer deaths), where proteasome inhibitors, prototypical negative proteostasis regulators, emerged as potent therapeutic agents, whose clinical use now extends to other cancers. However, despite substantial therapeutic advancements, MM remains incurable, due to primary and secondary drug resistance, calling for novel targeted therapies (2,3).

We recently discovered an essential role played by autophagy in long-lived bone marrow plasma cells, normal myeloma counterparts (4). We then challenged this role in MM, which proved exquisitely dependent on autophagy for organelle homeostasis and cell survival. In particular, we disclosed that MM cells depend on the prototypic autophagy adapter protein p62/SQSTM1 for survival, proteostasis, and proteasome inhibitor resistance (5). Dissecting the exact functions of p62 in MM cells holds promise for the informed design of novel potent targeted therapies (6).


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