Multiple Myeloma- 19s proteasome cap subunit

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For newly diagnosed myeloma patients, Velcade (bortezomib) can work wonders aka keep you in remission for years. Velcade is a class of chemotherapy drug called a proteasome inhibitor.

The article linked below explains that if a MMer has a 19s proteasome cap subunit, he/she may not respond to Velcade very well. See the green line in the graph on the right below- “19s suppressed” clinical outcomes fall below other MMers.

The good news is that several of the multiple myeloma cancer coaching (MM CC) integrative therapies have been shown to “enhance” Velcade and to “overcome resistance” of myeloma to Velcade.

Naturally occurring mechanism of cancer drug-resistance may itself be a treatment target

” Suppression of 19S proteasome subunits marks emergence of an altered cell state in diverse cancers

“However, recently, we discovered a counterintuitive mechanism by which cells can acquire resistance to proteasome inhibitors in vitro… Notably, the mechanism was clearly associated with poor outcome in patients with the blood cancer myeloma, where proteasome inhibitors are a mainstay of treatment.

Nevertheless, this new report reveals a strategy to address such resistance which may have broad utility. The researchers found that, beyond conferring resistance to proteasome inhibitors, the suppressed expression of proteasome subunits reflects a broad remodeling of the cell’s gene signature.”

Reducing 19S subunits protects human cancer cells from proteasome inhibitors

“Next, we asked if a simple reduction in the expression of 19S subunits could protect against the toxicity of proteasome inhibitors…

in contrast, the effects of knocking down several different 19S subunits had opposing effects, depending on the absence or presence of the inhibitor. In its absence, 19S subunit reduction had a fitness cost and decreased cell viability; in its presence, 19S subunit reduction provided a survival advantage and increased viability (Figure 2AFigure 2—figure supplement 1A–D).

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