About the Research

Research at the Center for Thoracic Cancers

 

Our team is working at the cutting-edge to rapidly bring discoveries from the laboratory to the clinic to improve outcomes for patients with lung cancer. Enclosed is a brief overview of key lung cancer discoveries made at the Mass General Cancer Center over the past decade. As you will see from the timeline, we are building momentum and making major discoveries at an increasingly rapid pace. These advances are having a real impact on patients with lung cancer throughout the world.

 

Targeted therapies have transformed the course of disease for some patients with lung cancer, and our team is constantly striving to develop new targeted strategies for patients who have not yet benefited from these advances. Currently, 49% of lung cancer patients do not have a known target. This means, they do not have any of the identified genetic abnormalities such as EML4-ALK, EGFR, BRAF and ROS. Without a target, physicians are unable to determine which therapies will be most effective.

 

We will not be satisfied until all lung cancer patients are able to benefit from more effective therapies. We are pursuing this goal through seven key approaches:

 

 

  • Identifying new therapeutic targets

In 2009, Mass General became the first cancer center in the world to offer genetic screening of lung tumors as a routine test with immediate clinical implications. Four years later, physician-scientists in the MGH Molecular Pathology Translational Research Laboratory have developed the next generation of clinical testing in cancer based on new, high throughput genomic technologies. As opposed to the current genotyping technology, which allows for genotyping ~60 of the most common mutations, next generation sequencing will make it possible to test the entire coding sequence of 1,000 cancer genes, including all genes currently known to play a role in cancers.

 

We are currently utilizing this new technology for research purposes, and we anticipate routine clinical application in 2014. By performing these tests on biopsies from patients with lung cancer, we aim to identify new genetic abnormalities that can then be matched with a targeted drug. The past 5 years have reinforced that this strategy works. The implementation of next generation sequencing into routine clinical care is a major priority for the Cancer Center and will be critical to additional targeted therapy successes.

 

 

 

  • Matching genetic targets with new drug compounds

Once new genetic abnormalities are detected through next generation sequencing, patient tumor samples are sent to the MGH Center for Molecular Therapeutics. Investigators in the center create human cancer cell lines from the fresh tumor sample and then screen these cell lines against over 200 new drug compounds to determine which genetically-defined subgroups within cancers are sensitive to new molecularly-targeted therapies.

 

  • Expanding clinical trials and changing standards of care

The work described above informs the selection of patients for subsequent clinical trials investigating these drugs. The thoracic oncology group is currently running 29 clinical trials and we plan to grow this number to 50 over the next few years. To do this, we are leveraging the infrastructure of the new Henri and Belinda Termeer Center for Targeted Therapies to expand the portfolio of Phase I – or first-in-human – clinical trials. Our goal is to get new and potentially life-saving drugs to patients who could benefit as quickly as possible. At MGH, we have a track record of translating discovery into new patient treatments that have become approved by the FDA and adopted as standard therapies throughout the world.

 

  • Combating drug resistance with second-line therapies

For lung cancer patients who have a known genetic mutation such as EGFR and ALK, we now have therapeutic agents that are to induce dramatic remissions. However, despite these initial responses, drug resistance typically develops within one to four years and tumor growth resumes. To better understand how drug resistance occurs, our team is conducting tumor biopsies at the time of diagnosis and again when resistance occurs during treatment. These studies are identifying new, previously unreported genetic changes in the disease and leading to the development of next-generation therapies capable of overcoming resistance, including combination therapies.

 

  • Employing the immune system as a new tool to treat cancer

New therapeutic approaches are needed for patients without known genetic mutations and for those patients with certain types of lung cancer, such as squamous cell lung cancer. One exciting new strategy has been to use drugs that stimulate one’s own immune system to recognize and combat cancer cells. These agents, known as PD-1 and PD-L1 inhibitors, have produced dramatic and durable responses in a subset of patients. In the last year, our team has rapidly expanded our portfolio of immunotherapy clinical trials, while simultaneously initiating broad efforts to identify biomarkers that may identify patients who are most likely to benefit from these therapies. This work is at the cutting edge of thoracic oncology and is revolutionizing how we think about and treat lung cancer.

 

  • Improving quality of life and outcomes

Another goal of our research is to discover better ways to care for our patients with lung cancer and their families to maximize their quality of life as they navigate their illness. In 2010, our team published groundbreaking work that demonstrated that initiating palliative care early in the treatment of lung cancer patients increases how long they live as well as their quality of life. The team continues to study interventions to improve cancer care and the wellbeing of patients and their families. This work is changing the way palliative care is perceived and changing standards of care around the world.

 

  • Detecting lung cancer early through screening

Early detection is critical to surviving lung cancer and recent studies show that lung screening with low dose CT scans saves lives. Over the past year, we have developed a comprehensive lung screening and nodule management program at MGH that combines the expertise of medical oncology, radiology, pulmonology and cardiothoracic surgery.  The team is preparing the program to meet the needs of our community with education, service and research to advance early detection efforts.

 

We have made incredible progress in a short period of time – resulting in countless lives saved or extended – and we could not have done this without the help of many people who share our commitment to the fight against lung cancer. Thank you again for your support.

 

 

 

Center for Thoracic Cancers Team

 

 

Christopher Azzoli, MD

Jeffrey Engelman, MD, PhD

Anna Farago, MD, PhD

Justin Gainor, MD

Rebecca Heist, MD, MPH

Elizabeth Lamont, MD, MS

Inga Lennes, MD, MPH

Lecia Sequist, MD, MPH

Alice Shaw, MD, PhD

Jennifer Temel, MD

Zofia Piotrowska,MD,MHS