We have known for some time that cancer is not a static, monolithic disease. Instead, we now think of cancer as heterogeneous. Each patient’s cancer may arise from widely dissimilar origins, even in patients with the same type of tumor.
Several studies in the last year have spelled out the extent of this diversity, which can be seen both as a tumor develops and within the same tumor types. Scientists working with Charles Swanton at Cancer Research UK published two meta-analyses that describe the prevalence of subclonal populations with unique combinations of genetic mutations across a wide number of cancers. Based on the extent of the observed heterogeneity, the authors saw a “need to stratify target therapy response according to the proportion of tumor cells in which the driver is identified and, moreover, indicate that certain pathways may be more actionable than others.”
Single cell genomic profiling holds the promise to deconvolute this complexity, and has made great strides in recent years. In 2014, Nicholas Navin summarized the progress, and predicted, “In the near future, single cell sequencing will begin to be applied to the clinic in early detection, prognostics, diagnostics, and therapeutic targeting, and thereby will have a direct impact on reducing morbidity in many human cancer patients.”
Recently, a group at Seattle’s Fred Hutchinson Cancer Research Center used single cell genotyping to demonstrate that subclones in acute myeloid leukemia patients evolve independently in response to therapeutics, and that this can lead to relapse. Howard Scher of Memorial Sloan-Kettering Cancer Center has reported that drug-resistant, sub-clonal tumor populations were present in patients in low numbers before treatment—and that the diversity of patients’ circulating tumor cell (CTC) subpopulations increased after each line of treatment.
In fact, at the ASCO Genitourinary Cancers Symposium this week, Scher is presenting data that suggests heterogeneity itself is a biomarker for predicting the outcomes for advanced prostate cancer patients. He reported that a low degree of CTC heterogeneity was correlated with a patient’s survival, while greater diversity signaled greater resistance to anti-androgen therapies. Furthermore, the presence of a newly discovered and rare subtype of CTC universally predicted the failure of anti-androgens and taxane chemotherapy. Identifying these types of biomarkers would be imperative before embarking on a course of treatment that in the best instance amounts to a waste of time, and in the worst case, allows a patient’s disease to terminally progress.
Without understanding the heterogeneous drivers of cancer, it is not surprising that outcomes improve in only a minor fraction of patients—even though global spending on oncology drugs reached $100 billion in 2014. Likewise, it does not require a leap of imagination to
