Tumor Heterogeneity: Implications for targeted therapy

Earlier this week, I had the chance to attend the "Tumor Heterogeneity: Implications for targeted therapy" conference at the Stanford Cancer Institute. (For a 6 min, 17 s summary of the topic, listen to Simon Tavare on ABC's Science Show.) Cancer is a complex disease - and tumors from different patients, multiple tumors from the same patient and even separate parts of the same tumor can look and behave markedly differently.

Treatment induces a bottleneck effect, where only some resistant sub-clones will survive and propagate to re-form a heterogeneous tumor. (Source: Wikipedia, by Lcchong - Own work. Licensed under Creative Commons Attribution-Share Alike 3.0 Unported license via Wikimedia Commons.)

For example, as Kimberly Allison (Stanford) pointed out, pathologist routinely look at breast cancer samples under the microscope to assess whether a tumor expresses high or low levels of the HER2 (ERBB2) protein. They struggle with summarizing what they see in a single score, because they frequently observe regions with high and low levels of HER2 in the same section.

The conference provided a broad range of topics, including technologies to characterize tumors at the single-cell level, the study of tumor evolution and clinical reports from physicians. Here are some of the main points I took away:

• late stage tumors contain many sub-clones, differing e.g. in the numbers and types of genetic lesions as well as response to treatment
• the degree of heterogeneity within a tumor is itself prognostic, e.g. more heterogeneity is often associated with a worse outcome
• subset of cells already carry mutations causing resistance to any specific cancer drug, and their expansion is associated with recurrence after single-agent therapy
• every tumor follows a unique evolutionary path, starting with early 'trunk' mutations followed by branching into sub-clones, which may compete, cooperate or simply co-exist.
• new technologies to detect tumors and characterize them over time, e.g. through blood draws during the course of treatment, offer opportunities to study the dynamics of cancer progression
• recent advances in the field of cancer immunotherapy, e.g. alerting the patient's immune cells to the presence of a tumor, may offer new therapeutic opportunities

In the coming days, I will summarize a few of my personal highlights from this meeting.