From Leukemia to ALK+ NSCLC: Finding a New Way to Overcome Drug Resistance

Juhi Kunde, Director of Patient Gateways and Science Marketing
Title banner with a photo of Dr. Qin

Read Time: 5 minutes 

Approximately 4% of patients diagnosed with non-small cell lung cancer (NSCLC) will have their tumors test positive for an ALK biomarker. This means the ALK gene in the tumor cells has fused with another gene (most commonly EML4). This fusion produces a hyperactive ALK protein that causes cancer cells to grow and spread. Patients with ALK-positive lung cancer are often treated with a class of targeted therapies called TKIs (or tyrosine kinase inhibitors), which aim to target the effects of the hyperactive protein and stop tumor growth.

However, ALK-positive lung cancer is known to eventually develop resistance to the TKI treatment and begin growing again. Understanding why this drug resistance happens and finding a way to overcome it are major areas of interest for ALK Positive, a patient-led advocacy group, and LUNGevity. To help address drug resistance in the ALK-positive lung cancer community, ALK Positive has joined forces with LUNGevity to support this important work with the ALK Positive / LUNGevity ALK-Positive Lung Cancer Research Awards. 

LUNGevity spoke to Angel Qin, MD, medical oncologist at the University of Michigan and one of the recipients of the 2022 ALK Positive Lung Cancer Research Awards, to understand what led her to study ALK-positive lung cancer and how her research could impact the lung cancer community.  

LUNGevity Foundation: Why is it important to support lung cancer research? 

Dr. Angel Qin: I think it is easy to forget that lung cancer is the number one cause of cancer-related mortality in the United States and around the world. It is a huge problem that affects everyone. In the past, there was a stigma around lung cancer. Many people thought that lung cancer was only related to tobacco exposure or other environmental factors. Other people thought lung cancer only affects the elderly. But we are learning that lung cancer affects all people from all walks of life. We are just beginning to understand lung cancer and all its complexities. That's why it’s critical to continue to support lung cancer research.  

LF: How did you become interested in this research project?  

AQ: I've always been interested in understanding why things don't work. Most people are very focused on when things do work, and of course, that's what we always want. But when it comes to treating patients with ALK-positive lung cancer, eventually the TKI will stop working and the cancer will grow again. This is a big question and a big concern for patients with ALK-positive lung cancer. 

I have a patient who was diagnosed with ALK-positive NSCLC. She is incredibly generous and focused on research and wants to understand how this cancer developed. She wants to know what the next treatment would be for her, and for others like her, when the TKI stops working.  

She gifted a large donation to the University of Michigan that allowed me to collaborate with an incredible team of scientists and researchers. We were able to start establishing collaborations with other institutions around the country and around the world to learn more about how ALK-positive lung cancer develops TKI resistance and how it can be treated.  

LF: Tell us about your ALK Positive / LUNGevity research project:  

AQ:  A Japanese study showed that a drug called gilteritinib (which is already approved for treating leukemia in the US) may be able to target ALK as well as other kinases that could be involved in ALK drug resistance in laboratory experiments. We reviewed these results and explored the idea more in the laboratory and found there was an exciting possibility to use gilteritinib to treat patients after their tumors developed resistance to lorlatinib. It is something we knew patients with ALK-positive lung cancer needed, so we wanted to try to bring gilteritinib to the clinic. That's where the idea for this project and this clinical trial came from.  

Not only do we have a chance to see if there are real benefits for patients who are running out of treatment options, but we’ve also built a lot of opportunities to learn more about ALK-positive lung cancer into our protocol. Patients who enroll in the clinical trial will also be sharing tissue and blood samples, which we’ll be able to use to sequence, study, and learn more about how their tumors respond to treatment.  

We expect the study to open in March 2024; if you follow the ALK Positive Facebook page you will get notified when it does. You can find the study details here.

LF: Why should the lung cancer community be excited about this work?  

AQ: Currently there are a handful of TKIs approved to treat ALK-positive lung cancer, but there's none approved beyond the third-generation TKI lorlatinib. We're really excited for the results of this study because we have the potential to bring powerful new treatment options to our patients and we will learn more about why tumors become resistant to treatment in the first place.  

LF: How has this research award impacted your work?  

AQ: This award has been incredible and I’m so grateful to ALK Positive and LUNGevity for this opportunity. Without this award, this research would not be possible. We all know that costs are going up and clinical trials are expensive. That’s why this award from ALK Positive and LUNGevity is so special. It has a focus on the patients and bringing treatments to patients right now, not ten years down the road. This gives us, as clinicians, a mechanism to do this potentially lifesaving work. It’s so empowering. 


More LUNGevity-supported research projects: