To improve the treatment of patients with metastatic cancer, responsible for 67%-90% of all cancer-related deaths, there is an “urgent” need to abandon the classification of tumors by organ of origin, such as colon, breast, or pancreas, in favor of one based on molecular characteristics.

This proposal was put forward 2 years ago in Nature by researchers led by Fabrice André, MD, PhD, head of the Research Division at Gustave Roussy, Department of Medical Oncology, Villejuif, France, and president of the European Society for Medical Oncology (ESMO), who has since championed the proposal at various medical conferences. He is a medical oncologist specializing in breast cancer and a professor of medicine at Paris-Saclay University, Paris, France.

In September 2025, André presented the argument as one of four lectures he delivered at the 27th Congress of Clinical Oncology in Buenos Aires, Argentina: “Today, the drugs we administer target a specific molecule, protein, or genomic alteration. Most of the therapies we used were biological therapies directed at a biological process. Therefore, we believe that there is no reason to continue thinking in terms of breast, ovarian, or colon cancer [once the disease has spread to other organs and curative options such as surgery or radiotherapy are no longer available]. Future classification should be based solely on biology.”

Molecular Framework

One of the central arguments for this position is that organ-based classification compels investigational drugs to be evaluated in sequential trials across individual cancer types rather than simultaneously enrolling all tumors that share a given molecular characteristic. André and colleagues argued that this model can delay regulatory approval and patient access to treatment by as much as a decade.

They illustrated this in the case of nivolumab, a PD-1 protein inhibitor. In a 2012 phase 1 study, nivolumab demonstrated activity across multiple tumor types with high expression of PD-L1, a protein that helps tumors evade immune attacks. However, the subsequent clinical development of nivolumab and related agents proceeded sequentially through different advanced cancer types: first melanoma, then lung cancer, then kidney cancer, and so on — rather than enrolling all tumors with high PD-L1 expression simultaneously, which would have been a more logical approach. As a result, “individuals with certain breast or gynecologic cancers that expressed PD-L1 had to wait 7-10 years to gain access to PD-1 inhibitors.”

A similar pattern was observed with olaparib, a PARP inhibitor that kills malignant cells harboring mutations in BRCA1 or BRCA2. The US FDA approved olaparib in 2014 for the treatment of advanced ovarian cancer. Approvals for metastatic breast, pancreatic, and prostate cancers followed in 2018, 2019, and 2020, respectively; however, by that point, André and colleagues estimated that approximately 300,000 individuals with these tumors had died without ever having access to a potentially beneficial therapy.

Beyond drug development timelines, the compartmentalization of hospital services, educational programs, scientific meetings, and clinical guidelines around the organ of origin “stagnates progress” in multiple ways, the authors argued.

“Hospitals are now organized by organ of origin, which means that a woman with metastatic breast cancer will be treated in an entirely different unit than a person with a biologically similar disease in another organ. This is somewhat strange because we should really be training experts in the biology of the disease to care for our patients,” André explained in a Nature podcast.

Classifying tumors by biology could also improve the understanding of molecular mechanisms and therapeutic approaches for oncology students and residents. André also identified a potential benefit for individuals living with cancer: If individuals better understand their disease, he hypothesized, they may better comprehend the choice of their treatment, which could facilitate engagement in the care process, reduce anxiety, and increase adherence to treatment.

Expert Pushback

André’s proposal met with a range of objections. In a response also published in Nature several months later, two German pathologists, Albrecht Stenzinger, MD, of University Hospital Heidelberg, Heidelberg, and Frederick Klauschen, MD, from Ludwig-Maximilians-Universität München, Munich, Germany, noted that cancer is not simply a collection of defective genes but an interaction between tumor cells and the tissue in which they grow. The organ of origin continues to shape cancer behavior, such that a drug effective against a specific mutation in melanoma may not produce equivalent results against the same mutation in colon cancer.

Others have raised concerns from the perspective of individuals living with cancer. “I think what is most important is for the general public to understand that we no longer treat cancer based just on where in the body it is located but also based on the subtype of the cancer so that we can target the treatment to more precisely match the cancer’s subtype. In addition, regulatory agencies need to follow science when it comes to biomarker-based clinical trials and drug approval. But there are commonalities among experiences of people with the same anatomical cancers (lung, breast, or prostate, for example) that cannot be ignored and make sense for people to share to gain support from each other,” wrote Claire Saxton, MBA, executive vice president of the Cancer Support Community, on LinkedIn.

Two Argentine clinical oncologists, speaking with Medscape’s Spanish edition, reflected on the relevance and practical applicability of biology-based rather than anatomy-based cancer classification.

Pedro Politi, MD, former associate professor of pharmacology, Facultad de Medicina, Universidad de Buenos Aires, and director of Equipo de Oncología Personalizada, Buenos Aires, described the proposal as an “oversimplification,” noting that solid human malignancies accumulate dozens of mutations of varying clinical relevance and can drive tumor progression in an adaptive, evolving manner.

“For whom is this view useful? For large pharmaceutical companies and academia, because it simplifies the work. And it can be beneficial if it accelerates development,” Politi said. He added that in 2015, the National Cancer Institute (NCI) launched the NCI-MATCH trial, which was designed to evaluate treatments on the basis of molecular profiles regardless of cancer subtype. Since then, the FDA has approved several tissue-agnostic systemic cancer treatments. “It is not a new concept,” he emphasized.

Implementation Barriers

However, applying such a model in routine clinical practice is far more complex. “Clinical oncologists are trained to manage a wide range of malignancies and stay current: Thinking from the mutation rather than the primary site does not benefit us or the person with cancer. Care is structured around specialties, each with its own knowledge, skill set, and procedures. I do not see how that structure could be dismantled; it would be deeply detrimental,” Politi said.

Claudio Martín, MD, head of Thoracic Oncology, Instituto Alexander Fleming, and head of the Oncology Section, Hospital María Ferrer, Buenos Aires, and president of the Asociación Argentina de Oncología Clínica, characterized André’s nomenclature proposal as “very innovative, but very difficult to implement in low- and middle-income countries.”

Across Latin America, significant barriers exist in performing comprehensive molecular profiling of all individuals with cancer, even when testing for mutations or biomarkers that have approved targeted therapies, Martín added. André acknowledged that the shift in classifying metastatic cancer would not occur unless more individuals gained access to tests that revealed molecular alterations in their tumor cells.

“Currently, most patients with cancer continue to be treated based on the clinical site of origin, either because molecular testing is unavailable or because their tumors do not carry molecular alterations that can be addressed with existing therapies. A substantially larger volume of molecular studies on tumors and their corresponding specific treatments is needed. It is a very interesting idea, but it cannot be applied abruptly,” Martín said.

Hybrid Approach

Speaking with Medscape’s Spanish edition, André clarified his original position. “While some scientific societies, such as ESMO, have begun working on this topic, which suggests academic interest exists, and the FDA also developed some guidance before the 2024 commentary was written, the challenge is that tumor origin may be important in certain circumstances,” he acknowledged.

“ESMO will present a scoring framework that integrates tumor-agnostic molecular alterations with tumor origin,” he added.

In a 2024 Nature podcast, André mentioned that a clinical trial was planned to prospectively demonstrate that the new approach to classifying cancers produces better outcomes for individuals with cancer.

When asked about the current status of the study.

“The trial is in its final phase of preparation. Ultimately, it will be a trial to assess whether generative AI can interpret the biology of cancer in each patient, independently of the organ of origin, using virtual twin technology — dynamic computational replicas of individuals with cancer designed to simulate the impact of therapies before they are administered,” André concluded.

André reported receiving institutional research funding from AstraZeneca, Lilly, Novartis, Pfizer, and Roche. Politi and Martín reported having no relevant financial relationships.

This story was translated from Medscape’s Spanish edition.