Molecular Medicine Israel

Opinion: Overcoming Cancer’s Complexities

Considering “targeted therapeutics” in the face of intra-patient heterogeneity

Cancer is a devious foe, revealing new complexities just as scientists find new ways to tackle them. A recent hope has been a new generation of “targeted therapeutics” that home in on specific molecular defects in cancer cells, promising more effective and less toxic therapy than imprecise chemotherapeutic agents. However, researchers are now realizing that they may have previously underestimated one of cancer’s oldest and best-known complexities: tumor heterogeneity. This may help explain the successes and disappointments with targeted therapeutics. It should also motivate a broader re-examination of research strategies.

Cancer can occur in any organ, although it occurs most commonly in the breast, lung, colon-rectum, and prostate. Researchers have long known about two types of microscopic heterogeneity lying beneath these macroscopic distinctions: inter-patient heterogeneity, involving differences among patients (e.g., different types of breast cancer), and intra-patient heterogeneity within a single individual’s cancer—including heterogeneity within a primary tumor, between the primary tumor and metastases, and among metastases. While there have been both success, and failures with so-called “targeted therapeutics,” our evolving understanding of intra-patient heterogeneity has added urgency to an old question: Can we treat complex tumors by attacking a limited number of molecular targets (and resulting pathways), or does intra-patient heterogeneity severely limit this approach?…

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