Confined to a wheelchair and unable to breathe without supplemental oxygen at 50 years old, Maria was running out of time—and hope. Her oncologist recommended hospice, but Maria, not ready to surrender to lung cancer, wanted a second opinion from another specialist.
After learning she had never smoked, the consulting oncology care team recommended treatment involving a new drug that was showing a great deal of promise for never-smokers with lung cancer. Within days, Maria was out of her wheelchair and breathing without supplemental oxygen. Her future remained uncertain, but for the moment, she had her life back—and with it, a renewed sense of hope and happiness.
“I will never forget her story,” said William Pao, M.D., Ph.D., who witnessed Maria’s second chance as a fellow at Memorial Sloan-Kettering Cancer Center years before becoming Head of Pharma Research and Early Development. “At the time, we didn’t know yet why never-smokers with lung cancer were responding well to the drug, but based on clinical data we saw in patients with similar profiles, we were able to put Maria on a treatment path that targeted her specific tumour type. Soon thereafter, we collaborated with others to identify the genetic basis of her tumour response so that we could routinely identify those most likely to benefit.”
With the tremendous strides in lung cancer screening and treatment made over the last decade, Maria’s story represents an early example of how effective a collaborative relationship between diagnostics and pharmaceuticals can be in the fight against lung cancer.
The journey to survival
Lung cancer is the most common type of cancer in the world. It is also the most aggressive, claiming the lives of 1.5 million people each year—more than breast, colorectal and prostate cancers combined.1 More than two-thirds of lung cancer patients are diagnosed at a late stage, after the cancer has spread to other parts of the body.2 Even with surgery, radiation therapy and chemotherapy, lung cancer survival rates are amongst the lowest of all cancer types.3 Left untreated, the disease can take someone’s life in seven months.4
Today, however, we have entered an era of new hope. “We have a much greater understanding of what takes place in lung cancer cells, how the immune system controls lung cancers and how to act on this new knowledge,” Dr. Pao said. “It’s an incredibly exciting time for lung cancer research and treatment, both in terms of diagnostics and drug development. New information is empowering us to help lung cancer patients like never before.”
Every cancer—every patient—is different
At the root of these groundbreaking advancements is a focus on understanding the genetics and disease pathways behind cancer. “We used to think there were just two main types of lung cancer, but today we know there are multiple different subsets,” Dr. Pao said. “If you take it even further—if you look at the genetic makeup—we now know everyone has individually different tumours.”
Genomic testing and advanced diagnostics can identify mutations in patients like Maria to predict the best therapy for the best possible outcomes, ultimately giving physicians and other healthcare professionals the ability to deliver truly personalised healthcare. In Maria’s case, she had an EGFR mutation (see inset box), which was the reason for her successful treatment results. Knowing any patient’s genetic footprint allows for greater precision when assessing risk, diagnosing disease, determining an accurate prognosis and assigning therapy. Today, experts can stratify and develop new, life-saving medications, and monitor patients throughout their course of treatment.
Examples of gene mutations that can be targeted
The anaplastic lymphoma kinase (ALK) gene rearrangement causes the formation of an ALK fusion protein, which drives the abnormal growth and survival of cancer cells.5,6 It is usually found in people who are non-smokers or light smokers.7 Patients with ALK gene rearrangement may benefit from a drug that specifically targets the ALK fusion protein, shutting down its signalling and leading to tumour cell death.
Epidermal growth factor receptor (EGFR) is a signalling protein that sits across the cell membrane.8 When epidermal growth factor (EGF) binds to EGFR, it triggers cell growth and division. In EGFR-mutant lung cancer, these mutations lead to sustained triggering of cell growth, resulting in the formation of cancerous tumours.8,9 Patients with this type of lung cancer may benefit from a drug that targets the mutant EGFR protein, shutting down its signalling and leading to tumour cell death.
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.10
ROS1 gene fusions account for 1-2% of NSCLC.10 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.10 Patients with ROS1 gene fusions may benefit from a drug that specifically targets the ROS1 protein.10
Read about one person’s experience with ROS1-positive NSCLC
Rearranged during transfection (RET) gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including NSCLC. Approximately 1–2% of patients with NSCLC harbour RET fusions.11 Patients with this genetic alteration may benefit from therapies that selectively target RET alterations rather than multi-target TKIs, due to enhanced clinical activity and better tolerability.12
Translating science into medicine
Collaborative research in the areas of diagnostics and pharmaceuticals is driving innovation that will potentially transform the lives of cancer patients and their families. Targeted therapies, used alone or in combination with other treatments, are helping to stop lung cancer cells from growing and metastasising. Immunotherapy continues to show tremendous potential by harnessing the power of the immune system to identify and destroy cancer cells; cancer immunotherapy has been shown to extend the lives of patients with metastatic disease by five years and beyond—much longer than with standard treatments, according to Dr. Pao. For patients whose tumours initially shrink on treatment but then become resistant, routine rebiopsies can reveal which drug may overcome resistance. Lung cancer remains a complex disease, but ongoing research, clinical trials and investigational medicines in the pipeline will continue to uncover answers that save and improve lives.
Although no single intervention is likely to cure cancer—and there is much work left to do—new possibilities are changing perspectives and prognoses. Experts like Dr. Pao and countless others are working to make lung cancer a chronic disease instead of a fatal one. Driven by the promise of the future and the rewards that come with giving patients like Maria the chance to experience more of life’s memorable moments, today’s collaborative relationship between diagnostics and pharmaceutical research is instilling hope where there once was none.
References
American Lung Association. Lung Cancer.
http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/learn-about-lung-cancer/what-is-lung-cancer/how-serious-is-lung-cancer.html . Accessed October 2017Ellis, PM, Vandermeer, R. J Thorac Dis, 2011 Wetp; 3(3):183-188.
American Lung Association. Lung Cancer.
http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/learn-about-lung-cancer/what-is-lung-cancer/how-serious-is-lung-cancer.html . Accessed October 2017Wao H,, et al. Systematic Reviews. 2013;2:10.
Choi YL, et al. Cancer Res 2008; 68:4971–4976
Roskoski Jr, R. Pharmacol Res 2013;68:68-94
Gridelli C, et al. Cancer Treat Rev 2014;40:300-306
Prenzel, N et al. Endocrine-Related Cancer 2001;8:11-31.
Britten CD. Mol Cancer Ther 2004;3:1335-1342.
Bergethon K, et al. J Clin Oncol. 2012; 30(8):863-70.
Drilon et al. Nat Rev Clin Oncol. 2018;15:151‒67.
Ackermann CJ, et al. Onco Targets Ther. 2019;12: 7857-7864