Why Prostate Cancer Behaves Differently: Scientists Identify 8 Genetic Profiles

Scientists have mapped prostate cancer mutations, categorizing them into eight distinct profiles, dubbed Integrated Mutation Signatures (IMS). This classification provides a framework for understanding the genetic mechanisms driving tumor aggressiveness and treatment response.

The Mechanics of Genetic Signatures

The study involved 903 patients, with an average age of 60, followed for up to seven years. Researchers integrated four categories of genetic alterations: single nucleotide variants, insertions and deletions (indels), structural variants, and copy number alterations.

From millions of mutations, eight distinct profiles emerged. The most prevalent include:

• IMS3 (linked to androgen receptors): Found in 39% of cases.
• IMS2 (damage from reactive oxygen species): Found in 21% of cases.
• IMS6 (replicative stress): Found in 19% of cases.

Metastasis Risks

Not all genetic profiles carry the same level of risk. Only four of the eight signatures were significantly associated with an increased risk of metastasis: IMS2, IMS3, IMS5, and IMS8. Notably, IMS5 is linked to the CDK12 gene (rather than BRCA1/2) and appears more frequently in patients of African descent. Replicative stress (IMS4 and IMS6) on its own does not elevate the risk of metastasis.

Therapeutic Guidance

An analysis of data from 240 patients with metastatic prostate cancer suggests that the IMS6 profile can serve as a biomarker for treatment selection:

• When IMS6 is active, androgen receptor inhibitor therapies demonstrate greater efficacy than traditional taxane-based chemotherapy.
• When IMS6 activity is low, there is no significant difference in effectiveness between these treatment modalities.

Study Limitations

The developed method is not yet ready for widespread clinical adoption. Approximately 8.6% of tumors did not fit any of the defined profiles, and 22% exhibited only age-related mutations. Furthermore, the conclusions regarding therapy are based on retrospective analysis. Prospective studies are required to validate these findings and establish them as standard treatment protocols.

Source: This commentary was adapted from an original Russian-language publication by Pravda.Ru.