Over the past century, the two main approaches to treating people with cancer — surgery and radiation — have focused on where in the body the tumour is. This has led to medical oncologists and other health-care providers, regulatory agencies, insurance companies, drug firms — and patients — categorizing cancers according to the organ in which the tumour originated. Yet there is a growing disconnect between classifying cancers in this way and developments in precision oncology, which uses the molecular profiling of tumour and immune cells to guide therapies.

More than ten years ago, for example, investigators in the United States showed in a clinical trial that the drug nivolumab could improve outcomes for certain individuals with cancer¹. In the trial — which included people with different ‘types’ of cancer (as conventionally defined), from melanoma to kidney cancer — nivolumab shrank some people’s tumours by more than 30%, but it had little or no effect on the tumours of others.

Nivolumab targets PD1. This is a receptor of a protein called PD-L1, which helps cancer cells to escape attack from the immune system. Of the 236 trial participants whose tumours could be assessed, 49 responded positively to the treatment. The key determinant was whether their tumour cells were expressing high levels of PD-L1.

The logical next step would have been to conduct clinical trials that tested the effects of nivolumab and other PD1 inhibitors in people with metastatic tumours that strongly express PD-L1, regardless of the organ in which their cancer had originated. But because of the way cancers are classified as breast, kidney, lung and so on, researchers had to conduct clinical trials sequentially for each disease type.

For about a decade, millions of people with tumours expressing high levels of PD-L1 were not able to access relevant drugs because trials had not yet been conducted for their type of cancer when they became unwell. Those with certain breast or gynaecological cancers expressing PD-L1 had to wait 7–10 years to access PD1 inhibitors.

A similar story has played out with most of the drugs tested in clinical trials over the past decade. These include PARP inhibitors, which kill tumour cells carrying mutations in the breast cancer genes BRCA1 and BRCA2. These mutations are now known to occur in multiple tumour ‘types’ as conventionally defined (see ‘Losing lives’), not just in breast cancers.

Metastatic cancers (those that have spread beyond the organ where they originated) account for around 67–90% of cancer deaths^2,3, and are almost always treated systemically, meaning with drugs that enter the bloodstream. To improve treatments for people with metastatic cancer, the community urgently needs to shift from using organ-based classifications of cancer to using molecular-based ones. This will require radical changes in how medical oncology is structured, conducted and taught.

LEGGI TUTTO https://www.nature.com/articles/d41586-024-00216-3?utm_source=Live+Audience&utm_campaign=c097e03c68-briefing-dy-20240205&utm_medium=email&utm_term=0_b27a691814-c097e03c68-49983888