Memorial Sloan Kettering researchers find a new SCLC subtype with normal Rb protein, potentially treatable with existing CDK4/6 inhibitor drugs.

Scientists at Memorial Sloan Kettering Cancer Center have discovered a new subtype of small cell lung cancer (SCLC) that retains a normal version of the retinoblastoma (Rb) protein, unlike typical SCLC where the Rb protein is usually mutated or lost. This unique subtype, present in about 6% of SCLC cases, shows increased aggressiveness and resistance to traditional chemotherapy. However, these Rb-proficient tumors have molecular traits that might make them responsive to CDK4/6 inhibitors, drugs that are already FDA-approved for other cancers.

The research team, led by pathologist Natasha Rekhtman, analyzed 208 SCLC tumor samples using genetic testing and immunohistochemistry to detect the Rb protein. They found that 14 samples had a normal Rb protein, while the majority had mutated or completely lost the protein. The presence of a normal Rb protein in these tumors suggests that they could be identified and potentially treated differently from other SCLC cases.

The identification of Rb as a biomarker for this SCLC subtype could guide personalized treatment, but current genetic tests like MSK-IMPACT® often miss mutations in noncoding regions of the RB1 gene. Therefore, more comprehensive testing methods are needed. Dr. Charles Rudin, co-corresponding author of the study, notes the importance of this finding, as CDK4/6 inhibitors could offer a new treatment option for patients with these aggressive Rb-proficient tumors. Further research and clinical trials are in the works to explore this possibility.

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