A new study published in EBioMedicine by the University of Virginia School of Medicine reveals a drug that may hinder cancer cell proliferation. The drug, called Pevonedistat, shows potential as a treatment for melanoma, and possibly other cancers as well.

When melanocytes, cells that give skin its color, mutate they can become cancerous and lead to melanoma. Approximately 80,000 Americans are diagnosed with melanoma each year, and once the cancer spreads the chances of survival greatly decline. A challenge that many patients face is therapeutic resistance.  Treatments such as chemotherapy and radiotherapy stop being effective when the cancer cells grow, mutate, and become resistant to them, thus new therapeutics are necessary to combat cancer.

Pevonedistat is a promising cancer treatment because in recent studies it stopped the progression of melanoma in mice that were implanted with melanoma cells.  Pevonedistat may be useful for people with melanoma who experience treatment resistance because it has different molecular targets than other drugs. Pevonedistat inhibits specific proteins, enzymes, and signal transduction pathways that are involved with cancer progression.  One such molecular pathway that is affected involves the protein called CRL4-CDT2-SET8/p21 that is encoded by the gene CDT2.  CDT2 is overexpressed in melanoma, as well as other cancers including  brain, breast, and lung cancers.  Overexpression of CDT2 leads to decreased overall health and chance of survival.  Cancerous cells become “addicted” to oncogenes, which are genes that can create tumor cells, and also to non-oncogenes.  Furthermore, this addiction can arise because the oncogenes create DNA replication stress from the uncontrollable division of cells,  and it is possible that the CDT2 alleviates the stress.  When the CDT2 gene expression is decreased or the gene is deleted, the replication of melanoma cells is inhibited, though the researchers are not sure exactly what characteristic causes the inhibition.
Currently, the drug is in clinical trials, and if these trials go well and the drug is approved, it could be a new therapy for melanoma. Tarek Abbas, the lead researcher, says, “we have great hope that this drug will have a very significant impact on melanoma in general.”


REFERENCES

  1. Paddock, C. (2016, September 12). Melanoma may be stoppable with drug that halts cancer cell proliferation. Retrieved September 20, 2016
  2. Benamar, M., Guessous, F., Du, K., Corbett, P., Obeid, J., Gioeli, D., . . . Abbas, T. (2016, August). Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma. EBioMedicine, 10, 85-100. doi:10.1016/j.ebiom.2016.06.023

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