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New Directions: What Innovations Are Coming Down the Pike for Lung Cancer?

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Innovations in medicine occur all the time. Some happen quickly, like the unprecedented speed with which the COVID-19 vaccines were developed. Others take more time to develop, as researchers leverage current knowledge and new ideas to develop novel pathways toward diagnoses, treatments, and survival for patients with a wide variety of diseases.

Each month, we dive deeply into lab reports, journals, and conferences to bring you the most highly anticipated innovations coming down the pike for one of the most dreaded diseases: cancer.

This month, in honor of Lung Cancer Awareness Month, our focus is on lung cancer. Among the new developments to keep an eye on:

A Drug That Works Against Breast Cancer May Help Fight Lung Cancer, Too
The tumors of some people with breast cancer express a high level of the protein HER-2, or there are HER-2 mutations that help the tumors grow and proliferate. The good news for people with breast cancer is that this protein can be targeted with the drug trastuzumab deruxtecan (T-DXd). And the good news for those with lung cancer is that HER-2 mutations have also been discovered in some people with lung cancer, especially those who are young, female, and nonsmokers.

In a small study presented at the European Society for Medical Oncology Annual Meeting, and published on September 18 2022 in The New England Journal of Medicine, more than half of the study participants with advanced HER-2-mutant non-small-cell lung cancer (NSCLC) responded to T-DXd, 92 percent of whom also experienced tumor shrinkage.

Next step: Two phase 2 studies are underway — one to evaluate a lower dose of T-DXd in lung cancer patients — and the other to evaluate its efficacy for targeting HER-2 mutations across other types of cancer.

A Heart Disease Drug May Also Be Repurposed Against Lung Cancer
Research presented at the Seventeenth International Conference on Endothelin on October 5, 2021 suggests that the protein endothelin (which is secreted by the endothelial cells lining blood vessels, in order to make them narrow) may also be a target for treating adenocarcinoma, the most common type of lung cancer.

Until now, endothelin overexpression has mostly been linked to heart conditions, such as high blood pressure, heart disease, and vascular problems. But new research has also linked overexpression of a form of endothelin to lung cancer. When endothelin was blocked in a research setting, researchers found significant declines in cancer cell growth, a decrease in their ability to spread within the body, and improved programmed cell death, a process by which cells with excessive damage self-destruct. (Cancer cells often ignore signs to self-destruct.)

Next step: Researchers now want to learn if new or existing drugs that target the endothelin receptor will work on lung cancer.

A Better Way to Predict Which Patients With Lung Cancer Will Respond to Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) are a category of immunotherapy drugs that have been considered game changers for lung cancer treatment, as they can substantially increase overall survival to 30 months or more.

But they come with a hitch: Only a fraction of patients actually respond to them. Predicting who will respond has been a work in progress. The most common way is to see whether patients carry a high level of a biomarker known as a PD-L1 protein. But it’s an imperfect tool.

Now researchers may have discovered a way to predict who will (or won’t) respond, by combining artificial intelligence (AI) and traditional precision medicine strategies, such as testing for the presence of biomarkers.

Leading the way is the OncoHost AI-based platform PROphet. In study findings presented at the 2021 European Society for Medical Oncology Virtual Conference, researchers examined blood samples for treatment response in 108 advanced NSCLC participants, 80 of whom responded to therapy.

Machine learning algorithms were used to delineate the groups, ultimately revealing that responders all produced changes in specific set of eight proteins (aka a protein signature) following immunotherapy, suggesting that patients producing these proteins would respond to ICI treatment, while those producing a different set might be resistant.

The hope is that platforms like PROphet can be leveraged in a clinical setting, allowing doctors to more accurately target treatment options (and potential beneficial outcomes) for patients with NSCLC.

Next step: Researchers hope to identify previously unanticipated targets for future therapeutic interventions for clinical trials.

A Vaccine that Targets EGFR may Treat and Prevent Lung Cancer
International researchers are studying several vaccines as a potential treatment for lung cancer. In general, these vaccines work by triggering the immune system to attack cancer cells in the body.

One particular vaccine, called CIMAvax-EGF, is already being used in Cuba. Studies conducted by Cuban scientists suggest it’s safe and may increase survival in patients with advanced disease. Results from one study revealed median survival among patients who received the vaccine was 12.43 months compared to 9.43 months for those in the control group.

CIMAvax-EGF works by targeting epidermal growth factor receptor (EGFR), a protein that’s overexpressed in lung cancer cells. The idea is the vaccine prevents EGF from binding to the receptor, which can stop tumors from growing and proliferating.

Currently, the vaccine is only available in the United States to people who participate in a clinical study. CIMAvax is an approved treatment for lung cancer in countries (other than Cuba), such as Paraguay, Peru, Argentina, Bosnia, Colombia, Kazakhstan, and Herzegovina.

Next step: A U.S. clinical trial is currently enrolling to determine if the vaccine can prevent lung cancer in high-risk patients or stop lung cancer from recurring in survivors. If it’s successful, CIMAvax could be the first preventative vaccine for lung cancer. Another study will examine how CIMAvax combined with other cancer therapies works as a treatment for patients with lung cancer or squamous head and neck cancer that has spread to other places in the body.

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