Forget lung, breast or prostate cancer: its name should change. A group of experts is asking for reflection on the name of tumors from the pages of the magazine 'Nature'. And it's not a question of 'toponymy'. According to the authors, specialists and researchers of the French Gustave Roussy Institute, in the era of target therapy and molecular profiling of tumors, the conventional way of classifying them, when metastatic, based on their organ of origin, risks denying people the access to drugs that could help them.
“An incredible revolution, unthinkable until recently. It is proposed to no longer name tumors according to the organ of origin, but on the basis of their molecular characteristics”, underlines in X Roberto Burioni, professor of virology at Vita Salute University San Raffaele. “Match point, and go Sinner”, comments Burioni with a joke and a reference to the title of his book, meaning that “today we fight cancer with very effective weapons. Victory is near”. We are, in fact, at the “match point”.
Over the past century, the two main approaches to treating people with cancer – surgery and radiation – have focused on the location of the tumor in the body. This led medical oncologists and other healthcare professionals, regulatory agencies, insurance companies, pharmaceutical companies – and patients themselves – to classify tumors based on the organ in which they originated.
However, there is a growing disconnect between this classification and developments in precision oncology, which uses molecular profiling of tumor and immune cells to guide therapies. More than a decade ago, for example, researchers in the United States demonstrated in a clinical trial that the drug nivolumab can improve outcomes in some individuals with cancer. The study included people with several 'types' of cancer (as conventionally defined), from melanoma to kidney cancer. Nivolumab shrank some people's tumors by more than 30%, but had little or no effect on others' tumors. Nivolumab targets Pd1, the receptor for a protein called Pd-L1, which helps tumor cells escape attack by the immune system. Of the 236 study participants evaluated, 49 responded positively to treatment. The determining factor was whether or not their tumor cells expressed high levels of Pd-L1.
The next logical step would be to conduct clinical trials testing the effects of this and other Pd1 inhibitors in people with metastatic tumors that strongly express Pd-L1, regardless of the organ in which the cancer originated, the experts review. But following the way cancers are classified — breast, kidney, lung, and so on — researchers had to conduct clinical trials sequentially for each type of malignancy. For about a decade, the article says, millions of people with tumors expressing high levels of Pd-L1 were unable to access the relevant drugs because trials had not yet been conducted for their type of cancer. Patients with certain breast or gynecological cancers that expressed Pd-L1 had to wait 7-10 years to access the drugs in question.
A similar story has occurred with most of the drugs tested in clinical trials in the last 10 years, the authors highlight, also citing Parp inhibitors, which kill tumor cells carrying mutations in the so-called 'Jolie' genes, Brca1 and Brca2. It is now known that these mutations occur in multiple tumor 'types' as conventionally defined, not just breast cancer, recall. And they add further: metastatic tumors represent approximately 67-90% of cancer deaths and are almost always treated systemically, with drugs that enter the bloodstream. “To improve treatments for these people, we must urgently move from the use of organ-based to molecular cancer classifications,” the researchers ask. “And this will require radical changes in the way medical oncology is structured, conducted and taught.” “.
Access to molecular testing must also be improved, they highlight, and “ensuring that all patients diagnosed with metastatic cancer receive molecular testing means reducing the costs of such testing. Currently, the approach costs about $3,000 per test in the United States and about $1,000 in Europe.” The current way of classifying cancer affects multiple aspects. “In some countries, patients are not reimbursed if they take drugs that have been tested in studies in which tumors are not defined by the organ from which they originated – experts report for example – Most oncology scientific societies, such as the American Society of Clinical Oncology (Asco) and the European Society of Medical Oncology (Esmo), publish their guidelines based on the organ of origin.Hospitals have departments for breast cancer, lung cancer and so on. This attachment to classifying cancer by organ of origin is blocking progress in many ways.”
“It goes against the scientific understanding that is emerging today”, insist the specialists. As an example, some lung tumors have mutations in the Egfr gene, some have mutations in the Met gene, others have translocations involving the Alk gene, and so on. “When regulatory bodies need to approve the use of treatments, molecular-based classifications are likely to become increasingly important as more and more drugs are developed using advanced biotechnology,” the experts predict. “In the coming years and decades, numerous 'layers' of information could be incorporated into comprehensive cancer characterizations that are unique to each patient, and this will open up increasingly personalized treatments. Classifying tumors based on their molecular characteristics,” the authors conclude. – would accelerate millions of people's access to effective treatments; it is also the first step towards precision oncology and a deeper biological understanding of how cancer works.”
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