Heinz-Josef Lenz, MD, Describes Future Potential of CDC37 and MAOB as Predictors of Response in mCRC

The needle might be further pushed forward for precision medicine through exploration of novel proteins such as CDC37 and MAOB in patients with metastatic colorectal cancer.

In an interview with CancerNetwork® during the 2022 American Society of Clinical Oncology Annual Meeting, Heinz-Josef Lenz, MD, a professor of medicine and J. Terrence Lanni Chair in Gastrointestinal Cancer Research at Keck School of Medicine as well as co-director of both the Center for Molecular Pathway and Drug Discovery and the Norris Center for Cancer Drug Development of University of Southern California (USC), highlighted the potential importance of MAOB and CDC37 as molecular markers predictive of response to treatment with targeted therapies in metastatic colorectal cancer (CRC).1,2

Both markers were assessed in patients who were treated as part of the phase 3 CALGB (Alliance)/SWOG 80405 trial (NCT00265850), the results of which indicated that patients with MAOB-low tumors achieved the most benefit from a cetuximab (Erbitux)–based regimen, and those with CDC37-dependent tumors could attain promising benefit from regorafenib (Stivarga) and bevacizumab (Avastin).

Transcript:

MAOB [holds particular promise] because there are inhibitors used for neurodegenerative diseases that would give us access to new treatment opportunities. We are planning to [test] that in preclinical mouse models. For CDC37 and HSP90, there are inhibitors of the heat shock protein that may not be as established as the inhibitors of MAOB. But there are ways to potentially interfere with the expression level of this chaperone protein. So yes, I think these are potential targetable new proteins that may impact the efficacy of our current chemotherapeutic regimens.

References

  1. Zhang W, Millstein J, Yang Y, et al. Predictive value of MAOB gene expression for targeted therapy in patients (pts) with metastatic colorectal cancer (mCRC) enrolled in CALGB (Alliance)/SWOG 80405. J Clin Oncol. 2022;40(suppl 16):3580. doi:10.1200/JCO.2022.40.16_suppl.3580
  2. Arai H, Yang Y, Millstein J, et al. Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer (mCRC). J Clin Oncol. 2022;40(suppl 16):3586. doi:10.1200/JCO.2022.40.16_suppl.3586