Posts Tagged ‘lung cancer research’

Lung Cancer Progress Made, But We’re Not There Yet

Lung Cancer (This blog was originally posted on September 29, 2014 on the American Association for Cancer Research website)

Luther Terry, the ninth Surgeon General of the United States, released his now seminal Smoking and Health: Report of the Advisory Committee to the Surgeon General of the United States on Jan. 11, 1964. The report, assembled by a brave and committed panel of independent physicians and scientists, definitively concluded that lung cancer and chronic bronchitis are causally related to cigarette smoking.

Fifty years later, genomic discovery and the rapidly accelerating fields of epigenetics, proteomics, metabolomics, and drug discovery have presented an armada of new options for patients with lung cancer. Computed tomography (CT) screening of high-risk individuals, particularly smokers, helps detect the disease in its early, more-curable stages more than 80 percent of the time. Breakthroughs in cancer immunology have led to the accelerated development of PD-1 and PD-L1 inhibitors, demonstrating remarkable and durable benefits in early clinical trials of lung cancer patients with advanced disease. But in 2014, five-year survival remains under 20 percent for patients diagnosed with lung cancer and more than 1.5 million people worldwide will die of lung cancer. Moreover, smoking rates, while down to 19 percent in the U.S., remain well over 30 percent in much of the rest of the world.

Despite the armada of new targeted medicines, cure remains elusive for the vast majority of patients diagnosed with this dreaded illness, and a significant number of never-smokers seem to contract this disease without any known risk factors. So why are we optimistic that major progress made in science can meaningfully impact lung cancer?

2014 has seen major strides in lung cancer research and treatment. Smoking cessation efforts have accelerated with the Food and Drug Administration’s (FDA) increased abilities to enforce regulations on tobacco products. Our understanding of lung cancer biology grows exponentially by the day. A number of exciting trials have been launched this year to test targeted agents in the adjuvant, postoperative setting, as well for therapy of patients with advanced stage disease. Exciting clinical trials have led to the approval of second- and third-generation agents targeting oncogene-driven tumors. A major initiative has been launched to target RAS, the most frequently mutated oncogene in all cancer, and a major driver of outcomes in lung cancer.

Substantial progress has been achieved this year in targeted therapy, stereotactic radiation, and immunotherapy of lung cancer. Collaborative work demonstrated that patients with metastatic lung cancer who were treated successfully by targeting their oncogenic drivers do better than individuals who were treated with standard approaches across several centers of excellence, and that work needs to be successfully translated in the community for all patients with lung cancer in the coming years. While emergence of resistance, triggered through enhanced survival signaling circuits, is inevitable in these highly complex tumors, our understanding of these escape circuits is accelerating rapidly. We are learning to combine improved imaging methods with superior technology to detect circulating tumor cells in order to identify and treat patients with disease earlier than ever before.

However, we have yet to show we can successfully intervene in lung carcinogenesis. In a large trial that we performed in the ECOG-ACRIN Cancer Research Group, we found that natural compounds are incapable of reversing the damage caused by ongoing tobacco smoke. We must ally smoking cessation and early detection, and enhance our understanding of the cause of disease in never-smokers. We need to develop potent but tolerable compounds that can reverse premalignant lesions in former smokers.

While the 2009 Tobacco Control Act has enhanced the FDA’s ability to regulate tobacco products in some key areas, such as marketing to minors, major obstacles regarding the regulation of cigars, water pipes, menthol, and particularly e-cigarettes have limited the FDA’s ability to more effectively regulate the menace of Big Tobacco. Indeed, the booming electronic cigarettes industry threatens to enable a whole new generation of smokers. Unless we act decisively to carefully regulate the use of e-cigarettes, the steady progress made in lung cancer research and therapy over the past few decades could be eroded. It is only when we effectively reduce smoking by enforcing the FDA’s control of all products and implementing tobacco control programs with real teeth while simultaneously unraveling and preventing the causes of lung cancer in never-smokers that we will truly start to make an impact, fulfilling Surgeon General Terry’s and, most importantly, our patients’ goals to make lung cancer a disease of prior generations, and a scourge no more.

About Dr. Khuri

Fadlo Khuri, MDFadlo R. Khuri, MD, deputy director of the Winship Cancer Institute of Emory University and Professor and Chairman of the Department of Hematology & Medical Oncology, Emory University School of Medicine, is a leading researcher and physician in the treatment of lung and head and neck cancers. He is Editor-in-Chief of the American Cancer Society’s peer-reviewed journal, Cancer.

Dr. Khuri’s contributions have been recognized by a number of national awards, including the prestigious 2013 Richard and Hinda Rosenthal Memorial Award, given to an outstanding cancer researcher by the American Association for Cancer Research.

An accomplished molecular oncologist and translational thought leader, Dr. Khuri has conducted seminal research on oncolytic viral therapy, developed molecular-targeted therapeutic approaches for lung and head and neck tumors combining signal transduction inhibitors with chemotherapy, and has led major chemoprevention efforts in lung and head and neck cancers. Dr. Khuri’s clinical interests include thoracic and head and neck oncology. His research interests include development of molecular, prognostic, therapeutic, and chemopreventive approaches to improve the standard of care for patients with tobacco related cancers. His laboratory is investigating the mechanism of action of signal transduction inhibitors in lung and aerodigestive track cancers.

Cancer Risk Dramatically Reduced Since Landmark Smoking Report Issued 50 years Ago

Dr. Fadlo KhuriFifty years ago this month, Dr. Luther Terry, Surgeon General of the United States, issued the landmark 1964 Surgeon General’s Report providing the first definitive proof that cigarette smoking causes both lung and laryngeal cancer. This announcement came after a committee of experts had worked for 18 months, reviewing more than 7,000 published papers and engaging 150 consultants.

The importance of this report and its findings cannot be overstated. Fifty years ago, we did not know that smoking definitely causes lung cancer and other diseases, only that smoking was associated with a higher risk of these diseases. Recognizing that the impact of tobacco on our national and, indeed, the world’s health was the major public health issue of the day, Dr. Terry assembled an unimpeachable panel of distinguished physicians and scientists. He chose individuals for the panel who were not only among the giants of medicine and science, but were also objective and could ensure the integrity of the report.

The report was based on what ranked as the largest and most careful review of the medical literature yet undertaken. Most importantly, the report was clear, evidence based and unequivocal. It showed beyond a shadow of a doubt that smoking caused both lung cancer and larynx cancer. The report concluded that cigarette smoking is 1) a cause of lung cancer and laryngeal cancer in men; 2) a probable cause of lung cancer in women; and 3) the most important cause of chronic bronchitis.

The impact of the report on public perception was astonishing. In 1958, only 44% of Americans believed that smoking seriously impacted health, according to a Gallup Poll. Ten years later, and four years after the report’s release, that number had climbed to 78%. The report also galvanized the anti-tobacco movement. Its findings have lent enormous credence to smoking cessation efforts over the last 50 years. In 1964, 52% of adult men and 35% of adult women smoked cigarettes. This had fallen to 21.6% of adult men and 16.5% of adult women by 2011.

Today, we are certain that tobacco causes some of the most widespread and devastating diseases in the world, including cancers of the lung, larynx (voice box), esophagus, mouth, throat and bladder, which together account for about 30% of the world’s cancer-related deaths. Tobacco is also a major cause of heart disease, emphysema and other diseases of the lungs and heart.

There have been several subsequent reports issued by the Surgeons General, the latest an eye-opening look at smoking behavior among the younger generation. This, like all prior reports, builds on that first landmark report from a great physician leader and his matchless panel of experts. The impact of their efforts on smoking in the US and the world is unquestionable. The debt that the world owes these 12 brave scientists has never been greater.

Author: Fadlo R. Khuri, MD, deputy director, Winship Cancer Institute

Want to learn more about the impact of the 1964 Surgeon General’s Report on smoking? View this video as Dr. Khuri further discusses the effect the report has had on the medical community.

About Dr. Fadlo Khuri
Fadlo R. Khuri, MD, deputy director of the Winship Cancer Institute of Emory University and Professor and Chairman of the Department of Hematology & Medical Oncology, Emory University School of Medicine, is a leading researcher and physician in the treatment of lung and head and neck cancers. He is Editor-in-Chief of the American Cancer Society’s peer-reviewed journal, Cancer.

Dr. Khuri’s contributions have been recognized by a number of national awards, including the prestigious 2013 Richard and Hinda Rosenthal Memorial Award, given to an outstanding cancer researcher by the American Association for Cancer Research.

An accomplished molecular oncologist and translational thought leader, Dr. Khuri has conducted seminal research on oncolytic viral therapy, developed molecular-targeted therapeutic approaches for lung and head and neck tumors combining signal transduction inhibitors with chemotherapy, and has led major chemoprevention efforts in lung and head and neck cancers. Dr. Khuri’s clinical interests include thoracic and head and neck oncology. His research interests include development of molecular, prognostic, therapeutic, and chemopreventive approaches to improve the standard of care for patients with tobacco related cancers. His laboratory is investigating the mechanism of action of signal transduction inhibitors in lung and aerodigestive track cancers.

Related Resources:

Lung Cancer: Not Just a Disease of Smokers

Cigarette smoking is the main risk factor for most patients who develop lung cancer; however, some patients who are diagnosed with lung cancer have never smoked a cigarette. Physicians today are seeing more non-smokers and light smokers with lung cancer. Why do these people get lung cancer?

We now understand that exposure to secondhand smoke can cause lung cancer, in fact, even passive exposure to tobacco smoke increases your risk for developing lung cancer. Secondhand smoke is responsible for 3,000 lung cancer related deaths a year in the United States, and there’s a 20 to 30% increased risk of developing lung cancer for nonsmokers living with a smoker. This is why so many cities have passed laws to limit smoking in restaurants, bars and clubs. Many workplaces are also becoming tobacco-free to protect the health of their employees.

Other environmental exposures besides tobacco smoke have been associated with lung cancer including chemicals used in some workplaces, such as asbestos, tar and soot and heavy metals like chromium, nickel and arsenic. There has also been an association with radon gas and lung cancer, especially in people exposed to high levels of radon, such as uranium miners. People who have been exposed to large doses of radiation, like atomic bomb survivors in Japan, also have a higher risk of lung cancer. It is still unclear how much of a factor air pollution plays in developing lung cancer.

Family history can also impact chances of being diagnosed with lung cancer. There is almost a two fold increased risk of lung cancer in a person with a family history and this risk is even higher if more than two relatives in a family have lung cancer. We still have not identified a particular gene that is passed on in these families that makes them more prone to lung cancer; however, at Winship Cancer Institute of Emory University, genetic testing is now given to every patient diagnosed with lung cancer to identify specific mutations in tumor tissue that may inform treatment decisions.

Research has identified genetic mutations in lung cancers from people who have never smoked or are/were light smokers. These mutations are not inherited, rather they originate in the lung tissue and create lung cancer. Interestingly enough, mutations in the epidermal growth factor (EGFR) and ALK genes have been found more frequently in lung cancer patients who never smoked. These patients can be treated with drugs that target these specific mutations.

Researchers at the Winship Cancer Institute are also involved in more extensive genetic testing of tumors to find other mutations that could explain why non-smokers develop lung cancer. Understanding more about these genetic changes and other factors will help us be able to treat all lung cancer, particularly those in non-smokers, with better, more personalized treatments.

About Dr. Pillai:

Dr. Rathi PillaiRathi Pillai, MD, is an Assistant Professor in the Division of Hematology and Medical Oncology. She joined the faculty after graduating from Emory University’s Hematology/Oncology fellowship program in 2013, where she served as chief fellow from 2012-2013. Dr. Pillai earned her medical degree from the University of Texas at Southwestern Medical School and completed her residency in internal medicine at Emory University. She is a member of the American Society of Clinical Oncology, American Association for Cancer Research, Eastern Cooperative Oncology Group, International Association for the Study of Lung Cancer, and the American College of Physicians. Dr. Pillai’s research interests are in novel therapies in lung cancer, including PD-1 targeted agents, and phase I drug development.

Related Resources: