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The way we classify metastatic cancers may need to be revamped, scientists have said, proposing instead a classification system that places the cancer’s molecular characteristics above the tissue of origin.
Traditional approaches to treating cancer, including surgery and radiation, target the organs in which the tumor is present. This practice formed the basis for classifying cancers according to the organ in which they originate. But most cancer deaths are the result of the disease metastasizing beyond the organ of origin; Individuals with metastatic cancer almost always receive systemic treatment with drugs that enter the blood.
What motivates the need for change?
Thanks to technological advances, doctors can also discover which genetic mutations are responsible in many cases for a tumor and attack them with drugs. All cancers of the same organ do not always share the same mutations, and these mutations are not limited to cancers of a single organ.
This advance in precision oncology requires that cancers be classified based on their molecular and genetic characteristics rather than the organ in which they originate, a team of researchers from France wrote in a paper. In this way, according to them, cancer patients can also access life-saving medications sooner.
Fabrice André, a medical oncologist at Gustave Roussy in France and lead author of the commentary, told this author that oncologists spend a lot of time testing new drugs in clinical trials sequentially, causing “delays in access to treatment.”
Have some drug trials been delayed due to sequential testing?
There is evidence to support this view. A 2012 clinical trial in the US investigating the drug nivolumab included people with different types of cancer, including melanoma and kidney cancer. Nivolumab targets the receptor for a protein found on some tumors. It improved symptoms in people with tumors with that particular protein.
The next logical step would have been to test nivolumab in people with tumors that expressed the protein regardless of where the cancer originated. But since cancers are classified according to their organ of origin (breast, kidney, lung, etc.), researchers had to perform trials one after another for each type of cancer.
As a result, for many years, people with tumors that expressed that particular protein could not access nivolumab because the drug had not been tested for their specific type of cancer.
Most drugs tested in clinical trials in the last decade have a similar story.
How else can the new plan help patients?
Naming cancers based on their biology rather than their anatomy “will reduce the time needed to conduct clinical trials,” Dr. André said, “because only a few randomized trials are needed, rather than testing the drug in each disease defined by the organ of origin.”
Mumbai Oncocare Center consultant medical oncologist and haemato-oncologist Kunal Jobanputra agreed. A trial of a drug targeting a particular genetic mutation will cover all cancers with those mutations. “A positive effect could be that trials will take less time to perform,” he said.
According to Dr. André, the revamped classification system could also help patients understand the rationale for their treatment. For example, two people may have the same cancer but not the same therapy because the biological mechanisms underlying their tumors are different. This can confuse patients, he said.
“Naming cancers with biological mechanisms would decrease such heterogeneity and also help the patient better understand the rationale for their therapy.”
Doctors often educate their patients about the molecular characteristics of their cancers, Dr. Jobanputra said. “When the connotation changes, the prognosis changes, the cost of treatment changes.
“We are moving towards a more personalized experience [treatment] focus,” he added.
What will it take to reclassify cancer drugs?
Some changes have also become evident in recent years in the approval of certain medications by regulatory agencies. In 2017, for example, the United States Food and Drug Administration (FDA) approved the use of the drug pembrolizumab to treat people carrying a certain mutation regardless of the organ in which the cancer originated. After this, the FDA also approved the use of some other drugs based on their biological objectives.
For different types of cancer to be reclassified in this way, regulatory agencies, scientific groups and insurance companies will also need to clarify when a drug must be approved based on its molecular target. The FDA is working on a guideline to that effect.
A particularly important requirement is that institutions establish teams that focus on analyzing patients’ molecular profiles regardless of cancer type, the researchers wrote in their paper. Medical students should be trained to understand the molecular basis of cancers rather than memorizing the characteristics of primary tumors.
Are there obstacles to implementing the plan?
Finally, this proposed change to classifying cancers cannot happen unless patients can access tests that reveal molecular alterations in their tumor.
This is particularly relevant in the Indian context, where we must take the proposed change with a pinch of salt, Dr. Jobanputra said, as most patients cannot afford genetic testing. These tests currently cost between Rs 7,000 and Rs 40,000 in Indian laboratories and up to Rs 3 lakh abroad. The availability and accessibility of genetic testing should be broader. “Only then can we jump to this diagnostic nomenclature.”
The proposed classification system is also not without flaws, Dr. Jobanputra added. Unless trials conducted based on molecular signatures have a significant number of patients with each type of cancer, they could generalize the results to all cancers.
We also cannot completely eliminate organ-level information, because disease location is an important factor in outcome, regardless of genetic mutations, he continued. For example, lung and brain cancers with the same mutations will continue to behave differently.
But “if done correctly,” the new nomenclature “can improve accessibility to medications,” he said, although this change will occur only gradually.
Dr. André agreed. “It will probably take a few decades. “There is some important research to do in terms of testing methodology before moving in that direction.”
Sneha Khedkar is a biologist turned freelance science journalist based in Bengaluru.