When Narjust Florez’s mother told her physicans that she had problems with her vision, they dismissed them as being due to cataracts. They were wrong. Florez’s mother had lung cancer, which had spread to her eyes. Despite her repeated medical visits and being highly educated and fully insured, her cancer was repeatedly missed. “My mum is a lawyer and still being gaslighted,” says Florez. “Imagine what it must be like for a regular person.”
Florez, a physician-scientist at the Dana- Farber Institute in Boston, Massachusetts who specializes in lung cancer in young people and women, has collected many similar stories. Studies show not only that women are routinely being diagnosed too late, but also describe lung cancer in women as an epidemic in some populations1. Yet lung cancer is still generally considered a disease of men.
Nature Outlook: Lung cancer
“When we talk about lung cancer, we always think about it as a disease of men, but actually there are more women with lung cancer than men,” says Daniela Molena, who studies lung cancer in women at the Memorial Sloan Kettering Institute in New York City.
Molena and other researchers suggest that lung cancer in women should be seen as a distinct disease, one driven by a complex interplay of biological sex differences and gender-based factors that researchers and clinicians have mainly overlooked. This oversight has translated into clinical practice that fails women at every turn: screening guidelines that have historically marginalized women, clinical trials in which women are under-represented2, inappropriate drug dosages and treatment regimens, and diagnostic delays that cost lives. “It’s just, unfortunately, inequalities from diagnosis to the moment of death,” says Florez.
Indeed, although incidence and mortality rates in men have been declining over the past three decades, lung cancer is overtaking breast cancer to become the leading cause of cancer deaths in women in many countries.
The trends are particularly alarming among younger women. In 2018, researchers reported that the incidence of lung cancer in white and in Hispanic women aged 30–49 had outstripped that in young men in the United States3. Tobacco use alone can’t explain this trend; women are developing lung cancer despite smoking less than young men do.
Why women?
Owing to the different roles that societies ascribe to an individual’s sex, women and men are exposed to different sets of risk factors. In many parts of the world, women do most or all of the cooking, exposing them to carcinogens released when oils are heated or coal and wood are burnt in poorly ventilated spaces. And because traditional gender roles result in women spending more time indoors than do men, women who do not smoke are disproportionately exposed to second-hand tobacco smoke at home or in the workplace.
Moreover, physiological differences between women and men mean that women respond differently to tobacco smoke. “If a man smokes one pack of cigarettes every day for 30 years and develops lung cancer, a woman requires only 20 because we have different metabolism of the carcinogens of tobacco in the liver,” says Florez. Studies suggest that sex differences in DNA-repair capacity might make women more prone than men to tobacco-induced damage1. The nature of this damage differs too. Women are significantly more likely than men to have carcinogenic mutations in genes such as EGFR and KRAS.
Hormones probably also play a part. Oestrogen receptors are expressed in many lung cancers, and oestrogen seems to influence gene expression in tumour cells. Florez’s team is investigating the use of contraceptive pills by teenage girls, and hormone supplements given to food animals, as possible explanations for the rise in lung cancer in young women.
Fundamental differences are also emerging in the core molecular biology of male and female cells. Camila Lopes-Ramos, a computational biologist at Harvard Medical School in Boston, Massachusetts, has modelled how genes involved in vital cellular pathways, such as cell proliferation, immune response and drug metabolism, are regulated differently in both lung tumours and healthy lung tissue in men and women4. In women, she and her colleagues have found, genes involved in these processes are the focus of more-intense attention from gene-regulation proteins than they are in men. In another study of 29 types of tissue5, the team found that in tissues in which cancer is more common in women, cancer-related genes were more intensely regulated; for male-dominated cancers, the opposite was true.
This means that even if a gene’s expression looks the same in men and women, the regulatory wiring underpinning that expression can be markedly different, says Lopes-Ramos. The disparity could also affect responses to treatment. Cancer genes that are targeted with anticancer drugs showed sex differences in how they are controlled, suggesting that sex-specific dosing or selection strategies could be warranted. “The clinical implication here is huge,” says Lopes-Ramos. “We’re ignoring a lot of the biological sex differences.”
Research disparities
Yet women are still less likely than men to be included in lung cancer screening trials. The outdated view that lung cancer mainly strikes in old, male smokers means that women tend not to get invited to participate in trials. For example, only 16% of participants in the NELSON trial — the largest in the world to study the efficacy of using low-dose computed tomography (CT) screening — were women. Social barriers, such as family caring responsibilities, are also an issue when recruiting women, says Molena.
Things are improving: the US National Lung Screening Trial, for example, fared better, with about 40% female participants. But screening guidelines have historically excluded up to 80% of women who go on to be diagnosed, and new ones still miss the majority of them.
The supreme irony is that women benefit more than men from screening: it reduces women’s mortality after ten years by 33%, compared with only 24% in men6. Molena explains that this is because the disease is slow-growing for longer in women, so they will be in better shape physically when diagnosed by screening — especially if they are non-smokers.
Currently, women’s tumours are often diagnosed incidentally, during examinations for other problems. At the 2025 World Conference on Lung Cancer in Barcelona, Spain, Florez and her team presented evidence that women with lung cancer symptoms are often misdiagnosed with anxiety. “I had a lot of patients leaving the emergency room with a prescription for [the tranquillizer] Xanax and no diagnosis of lung cancer,” says Florez. “Most of them are diagnosed at stage 4 when it’s not curable.”
Treatment inequalities
The pattern of exclusion extends to trials of treatments too. Women experience significantly higher rates of severe adverse events from treatments such as chemotherapy, including higher rates of nausea, vomiting, hair loss and neurological problems, than do men. These differences might be related to how women and men metabolize anticancer drugs differently. Yet dosing regimens are still based on the outcomes of clinical trials in which male participants predominate.
In unpublished work, Molena and her team studied 145,000 people who underwent lung cancer surgery, comparing factors such as age, race, smoking history, tumour characteristics, genetic mutations and survival outcomes. The results backed up a smaller study by the same team7, which found that the women were often non-smokers and that women did not respond in the same way to immunotherapy as did men. Consequently, the team suggested that lung cancer in women could be seen as a distinct disease — a view that other researchers share. One reason for raising the idea, says Molena, was “to incite some curiosity in terms of looking at this disease a little bit differently” and prompt discussion about fresh approaches.
Lopes-Ramos agrees with the idea of what she calls “sex-aware precision medicine”, but cautions that there is still a lot of overlap between men and women. “It’s thinking about the biological sex differences across all areas of basic research” and how these differences affect clinical practice, rather than holding the view that there is one version of lung cancer for men and another for women, she says.
Other lung cancer studies have shown that immunotherapy outcomes are dependent on sex, with women experiencing more adverse side effects than do men. Some studies suggest that immunotherapies are less effective in women unless combined with chemotherapy. One explanation, Molena suggests, could be that women’s tumours more often harbour mutations in EGFR. Such tumours respond more poorly to immunotherapy, but react well to drugs targeted at the EGFR protein. This is important for women: if they are more likely to have lung cancer driven by these gene mutations, they should be treated with something that targets the mutations, says Molena. Establishing this for sure would require trials to assess how tumours with similar molecular profiles in women and men respond to a given treatment. Such trials are not yet under way.
“Women are screwed,” says Florez. “We get more of the cancer, we get less responses to therapy and we’re also less likely to be included in clinical trials.”
Recognition of the problem is increasing. In 2024, the American Cancer Society published a review of lung cancer in women, aiming to collate all of the disparities into one call to action8. Still, even this is a limited advance. “It’s more of a catalyst than the actual change itself,” says Leah Backhus, a thoracic surgeon at Stanford University in California and chair of the group that produced the plan.
But Backhus points to one concrete initiative that came out of the group’s broader work: a successful pilot programme at three US institutions to test whether lung cancer screening can be bundled with routine mammography appointments, thereby reaching women who might otherwise never be offered a CT scan. Targeting women in this way will be key to trial recruitment — as illustrated by the TALENT trial in Taiwan and by the FANS trial involving Asian American women.
Patient voices, too, will be invaluable for drawing clinicians’ attention to the shortcomings of the current system. “We’re not just talking about trends and statistics,” says Backhus. “These are actual people whose diagnosis and treatment were not as they should have been.”
