I consider myself really privileged. As Director of Research and Policy, I get to attend scientific conferences and report out on the latest research into the early detection and treatment of lung cancer. You may have seen several of my blogs about conferences I have attended. While all of the conferences are interesting, the annual American Association for Cancer Research conference has a special place in my heart.
Being the nerd that I am, I love hearing about advances in pre-clinical research. Scientific conferences focus on different aspects. The annual ASCO meeting, for example, is clinically geared and you will hear a lot about clinical trials. The annual AACR meeting, on the other hand, is focused primarily on basic science and pre-clinical research. And to put things into perspective: rigorous basic science research lays the foundation for groundbreaking clinical research. This year, more than 21,000 participants from 80 countries attended, making this the largest meeting in AACR’s 110-year history. I was delighted to see lots of familiar faces: quite a few LUNGevity awardees and Scientific Advisory Board (SAB) members presented their research.
Representing the only lung cancer nonprofit with a programmatic focus on early detection, I was especially thrilled to see several talks on early detection and lung cancer interception. LUNGevity SAB member Dr. Avrum Spira’s team from Boston University presented several significant findings. His team, in collaboration with major research centers in the US, is putting together a pre-cancer genome atlas (PCGA) for squamous cell lung cancer, a type of non-small cell lung cancer that develops in former and current smokers. The PCGA will help researchers define better tools for the early detection of lung cancer in high-risk individuals.
In addition, his team is developing pre-clinical mouse models for the interception of lung cancer. Cancer develops in a sequential process; normal cells acquire changes in their DNA and progress to form precancerous cells, then cancer cells. And intercepting cancer means catching the precancerous cells and stopping them from turning into cancer cells. Using mouse models that mimic how lung cancer develops in patients, Dr. Spira’s team will be able to test drugs that can catch lung cancer before it gets going! This work will be complemented by research from LUNGevity awardee Dr. Jennifer Beane from Boston University, who presented new data on how the immune system also changes when normal cells change to cancerous cells. Immune interception is definitely something to keep an eye out for!
Immune interception is the perfect segue into immunotherapy. SAB member Dr. Julie Brahmer from Johns Hopkins University presented long-term follow-up data from immunotherapy clinical trials in the second-line setting. Patients who showed a response to immunotherapy have a five-year survival rate that has surpassed historical (chemotherapy- treated patients) survival rates. This is the first evidence that responses to immunotherapy are long-lasting!
We also know that immunotherapy doesn’t work for everyone. Scientists are aggressively searching for biomarkers that will predict response to immunotherapy and help to identify patients who will benefit from it. Currently, the only biomarker used for patient selection is PD-L1. It is not a perfect biomarker, and other biomarkers such as tumor mutation burden (TMB) are being investigated. TMB is a measure of how many mutations (changes in the DNA sequence of lung cancer cells) are found in a patient’s tumor. Data presented at this meeting suggest that lung cancers with a high TMB may respond better to immune checkpoint inhibitors such as nivolumab. Another piece of the immunotherapy puzzle that is being solved is how cancer cells develop resistance to immunotherapy. I will make an honest confession—the shrewdness of cancer cells never ceases to surprise me! They develop elegant mechanisms to evade immunotherapy, such as turning on new invisibility cloaks or switching on pathways that are normally off. Scientists are already putting together pieces of this puzzle to stay a step ahead in the game! Combination therapies might be a potential solution to tackle acquired resistance to immunotherapy.
The greatest progress we have made in understanding how lung cancer cells eventually become resistant to their treatment is in the field of targeted therapies for adenocarcinoma patients. In her plenary talk, LUNGevity SAB member Dr. Alice Shaw, from Massachusetts General Hospital/Harvard Medical School, highlighted how our understanding of the tactics that cancer cells use to outwit targeted therapies has led to the development of more potent targeted drugs. Now, for patients whose tumors test positive for EGFR or ALK mutations, Dr. Shaw pointed out that we have a treatment algorithm—how doctors are ready with drug C when drug A or drug B fails. Soon, we will have similar algorithms for ROS1-positive patients. Tools to understand acquired resistance have also evolved. Convenient blood-based tests can predict if a patient will develop resistance to an EGFR inhibitor, helping clinicians to be ready with the next drug. Targeted therapies for other types of lung cancer, such as small cell lung cancer (SCLC), also continue to show promise. SCLC cells produce high amounts of proteins called PARP. Drugs that block PARP continue to show promise, in combination with other chemotherapy agents such as temozolomide.
The AACR 2017 presentations spanned cancer research from prevention to treatment. Let’s see what ASCO 2017 brings!
Dr. Basu Roy is LUNGevity's Director of Science Communications and Programs.