Keys to Unlocking Multiple Myeloma Resistance

Multiple myeloma resistance overcome

(RxWiki News) People living with the blood cancer multiple myeloma typically take two drugs in combination. The problem is these drugs don't work with every person and tend to fade in effectiveness over time.

Researchers are finding ways to combat this resistance.

A couple of new studies have detailed the molecular factors that result in multiple myeloma therapy resistance.

New drugs have been identified to overcome this resistance, and biomarkers have also been identified which could help in combining therapies.

"Ask if new drug combinations are available."

Frontline multiple myeloma therapy involves two drugs - Revlimid (lenalidomide) and Velcade (bortezomib) - which are used together with other medications.

When these drugs don't work or patients become resistant to them, it's important to identify what mechanisms are causing the resistance and target them, says lead investigator, Robert Orlowski, M.D., Ph.D., professor and head of the Multiple Myeloma Section in MD Anderson's Department of Lymphoma and Myeloma.

In one study, Orlowski's research team found the following:

  • The insulin-like growth factor (IGF-1) helps make myeloma cell lines resistant to Velcade.
  • IGF-1 receptors can be blocked with what's known as small hairpin RNA (shRNA) to restore the drug's effectiveness.
  • Another approach involved the experimental IGF-1 blocker OSI-906, which killed drug resistant cells without harming healthy ones.
  • Combining shRNA and OSI-906 killed even more myeloma cells.
  • Revlimid resistance was overcome by blocking another pathway.

In the other study, resistance to Revlimid was explored. Orlowski's lab had shown in earlier research that a protein CD44 plays a role in interfering with the drug, and its presence usually indicates a poor outlook for the patient.

The chemotherapy drug Vesanoid (all-trans-retinoic acid) can overcome Revlimid resistance and also decrease the level of CD44.

Researchers then combined Revlimid with an experimental drug FH535 to increase cell death in resistant multiple myeloma cell lines.

Findings from these studies were reported the results at the 53rd Annual Meeting of the American Society of Hematology.

Review Date: 
January 5, 2012