Researchers Uncover Cancer Metastasis Subtypes

Metastasis, the spread of cancer cells from the primary tumor to other parts of the body, is the cause of most cancer deaths. To develop new and effective treatment strategies, it is crucial to better understand the mechanisms behind metastasis. In a recent study published in the journal Cell Reports Medicine, scientists at Baylor College of Medicine have taken a closer look at the molecular pathways that cancer cells use during metastasis. By analyzing molecular data from over 3,000 patients and 4,000 tumors, the team identified four cancer subtypes according to the primary genes expressed.

One of the challenges of studying cancer metastasis is the presence of non-cancer tissue in tumor samples, which interferes with the molecular analysis of cancer cells. To overcome this challenge, the researchers used data from PDX (patient-derived xenograft) cancer models, where human cancer tissue is implanted in immune-deficient mice to grow into metastasis-like tumors. The data obtained from the PDX models allowed the team to define four cancer molecular subtypes in the metastasis-like samples, which are also present in patient metastasis and are broadly represented among different cancer types.

The tumors in the first subtype have extensive alterations in gene copy number, higher expression of both DNA repair genes and transcription factor genes such as MYC. This suggests that tumors of this subtype might be susceptible to MYC-inhibiting compounds or BET inhibitors currently under clinical evaluation. The second subtype has higher expression of genes involving metabolism, prostaglandin synthesis and regulation. Tumors in this group might be susceptible to COX-2 inhibitors. The third subtype has evidence of neuronal differentiation and high expression of genes EZH2 and BCL2. In this case, such tumors might respond better to EZH2 or BCL2 inhibitors. The fourth subtype has higher expression of immune checkpoint and Notch pathway genes, suggesting that these tumors could be affected by immunotherapy.

The study’s results have important implications for therapy, as the researchers found that, in most cases, primary and metastatic tumors were not of the same subtype. This suggests that primary and metastatic tumors may need to be treated differently, providing valuable insights for developing personalized treatments for metastatic cancer.

This study is a significant step forward in understanding cancer metastasis and its molecular underpinnings. The identification of four cancer molecular subtypes provides a foundation for the development of personalized treatments for metastatic cancer and has the potential to improve patient outcomes.