Category: 8. Health

June is Men’s Health Awareness Month. In recognition of this event, we spoke with Justin Dubin, MD, a urologist at Memorial Healthcare Systems in South Florida, about the current landscape of care in men’s health.

Dubin acknowledged that while progress has been made in normalizing conversations around issues such as erectile dysfunction, stigma around men’s health conditions remains a large concern in 2025. This has created an opportunity for artificial intelligence (AI) to take off in this space, with many men turning to large language models to find information.

“Men being men, we always want to fix problems ourselves,” Dubin explained. “And instead of going to talk with a provider, they go online. Initially it was social media. It has advanced to things like podcasts and naturally, Dr. Google, Dr.TikTok, and has now progressed to Dr. ChatGPT.”

Dubin touched on both sides of this issue, highlighting both the challenges with AI in health care as well as the potential opportunities for use in the men’s health space.¹ One such opportunity is in patient education. Technology such as ChatGPT gives patients the chance to take ownership of their health, allowing them to better understand health concerns, ask informed questions, and feel more confident about seeking care.

For health care professionals, this also means a shift in the way they’re delivering care, with a new focus on making sure that men are using the right tools.

“In general, this is a very interesting time in men’s health. I think a lot of men who [were] always interested in having autonomy over their education and how they learn and autonomy over their bodies, finally have an opportunity to do that in a good way,” Dubin concluded. “You have a lot of information and a lot of opportunity for autonomy at your hands. It’s just really having the appropriate guidance to do so.”

REFERENCE

1. Panken EJ, Patel AU, Schammel J, Dubin J. Man and machine: exploring the intersection of artificial intelligence and men’s health. Curr Opin Urol. 2025;35(3):236-242.

doi: 10.1097/MOU.0000000000001274

As the first phase 3 trial to investigate an Fc-silent, anti-TIGIT agent in patients with solid tumors, the STAR-221 study (NCT05568095) may further clarify the therapeutic role of domvanalimab plus zimberelimab (Sepalizumab) and chemotherapy in patients with gastric cancers, potentially reshaping first-line treatment paradigms, particularly for PD-L1–positive disease, according to Kohei Shitara, MD.

STAR-221 is investigating the combination of the TIGIT monoclonal antibody domvanalimab, the PD-1 inhibitor zimberelimab, and FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) vs nivolumab (Opdivo) plus FOLFOX or CAPOX in the first-line setting for patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.¹ Overall survival (OS) serves as the primary end point. Secondary end points include progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), safety, and quality of life outcomes.

The initiation of STAR-221 is based on positive findings from the phase 2 EDGE-Gastric trial (NCT05329766).² Updated findings from arm A1 of the study showed that in all evaluable patients with first-line, locally advanced unresectable or metastatic gastric/GEJ/esophageal adenocarcinoma (n = 41), at a median follow-up of 13.9 months, the confirmed ORR with domvanalimab plus zimberelimab and FOLFOX was 59% (95% CI, 42%-74%). Among patients with a PD-L1 tumor activity positivity (TAP) score of at least 5% (n = 16), this rate was 69% (95% CI, 41%-89%). Among those with a TAP score of less than 5%, the ORR was 50% (95% CI, 29%-71%).

“Maybe the benefit [will be limited to] patients in the PD-L1–high population, but we should see the actual data [from STAR-221],” Shitara said in an interview with OncLive®. “If we have positive findings, this may give us important insight about the structure of the antibody and whether Fc-silent or Fc-activated [agents] give us different stories [in the context of] past negative trials.”

In the interview, Shitara discussed the mechanism of action and clinical activity of the TIGIT-targeted agent domvanalimab; preclinical and phase 2 data that support the continued investigation of domvanalimab plus zimberelimab and chemotherapy in patients with gastric/GEJ/esophageal cancers; and the potential clinical implications of results from STAR-221, which may be influenced by PD-L1 status.

Shitara is the director of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan.

OncLive: How do domvanalimab and zimberelimab work alongside chemotherapy to elicit antitumor responses?

Shitara: The important target molecule is TIGIT, especially for this combination. TIGIT is an inhibitory checkpoint receptor expressed on various types of immune cells, especially exhausted CD8 cells and regulatory T cells [Tregs], where it usually competes with activating molecules, such as CD20 and CD26, for binding its ligands. If there is TIGIT expression, this usually leads to inhibition of a specific immunophenotype like T cells, Tregs, and natural killer cells. Importantly, [TIGIT] is usually observed with other immune checkpoint molecules, such as PD-1 and LAG-3 [inhibitors]. It is expressed at a relatively later stage of exhaustion. That’s why blocking TIGIT has emerged as an attractive strategy in cancer immunotherapy. This is usually combined with anti–PD-1 and –PD-L1 agents.

An important aspect [of some] TIGIT antibodies is [the] Fc-maintained or Fc-activated [state, which] retains Fc receptor binding capabilities, leading to antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity to deplete TIGIT-expressing immune cells. For example, an Fc-maintained IgG1 antibody may deplete Tregs. This may be good for antitumor response, but it may also increase autoimmune toxicity because of the depletion of Tregs.

Another class of agents is the Fc-silent TIGIT antibody, which is engineered to lack Fc receptor engagement. It doesn’t deplete Tregs—instead, it [mainly] enhances the expansion of effector cells. On the other hand, if Fc is maintained, there is also a risk of depletion of activated effector cells. There are always pros and cons for this kind of structure.

In preclinical studies, there’s a good paper for both classification of Fc-silent and Fc-maintained antibodies. This was published in Cancer Research and supports that Fc-silent IgG1 antibodies for TIGIT may be better compared with Fc-maintained [agents]. However, another group published a different paper in Nature that supports that Fc-activated TIGIT antibodies are better, especially regarding depletion of immunosuppressive cells, like Tregs.

Based on these preclinical studies, TIGIT inhibition is attractive. However, there are 2 types of anti-TIGIT antibodies. Domvanalimab is mainly an Fc-silent IgG1 antibody. This may not deplete inhibitory cells, but [it may] mainly activate exhausted effector cells. Because of its lack of depletion of Tregs, the toxicity profile is expected to be feasible. This is usually combined with the anti–PD-1 [agent] zimberelimab. Zimberelimab is an IgG4 monoclonal antibody [with a mechanism of action] similar to that of nivolumab and pembrolizumab [Keytruda]. This combination has been tested in various clinical trials.

What phase 2 data contributed to the rationale for STAR-221?

This combination’s development is further supported by results from the ongoing EDGE-Gastric trial. This is a first-line gastric cancer trial [planning] to enroll approximately 40 patients to test domvanalimab and zimberelimab in combination with a cytotoxic FOLFOX regimen. Initial data were presented at the 2024 ASCO Annual Meeting and showed an ORR of 59% in the entire population, with a median PFS of 12.9 months. Although the small sample size is a relatively major limitation of the study, [the findings], in direct comparison with [those from] previous pivotal trials like the phase 3 CheckMate 649 [NCT02872116] and KEYNOTE-859 [NCT03675737] studies, suggested an increased ORR and longer median PFS.

The subgroup analysis [data] also support [population] enrichment by PD-L1 status. This TIGIT-directed domvanalimab/zimberelimab/chemotherapy combination seemed to work better in patients with high PD-L1 expression, such as a combined positive score [CPS] or TAP score of 5% or higher. This is in line with our expectations, because TIGIT is usually co-expressed with other checkpoints like PD-1 [T] effector cells. Additionally, the safety profile looks manageable; because of a lack of Treg depletion, autoimmune reactions seem to not be increased.

The phase 3 STAR-221 trial is ongoing to test domvanalimab/zimberelimab in combination with first-line FOLFOX or CAPOX vs the current standard of chemotherapy plus nivolumab in the first-line setting. We needed to test PD-L1 status before patient enrollment. Patients could be enrolled regardless of PD-L1 status, but stratification by PD-L1 status was important, considering the mode of action [of the combination demonstrated in] the subgroup analysis of the phase 2 study. That’s why PD-L1 TAP score was included as one of the stratification factors for the primary end point for OS in this study. Subgroups will also be tested according to TAP score or CPS status. Enrollment [to STAR-221] is completed, and we are waiting for survival follow-up and analysis.

Concerning the current other trials for TIGIT-targeted therapy, unfortunately, no phase 3 trial has shown the benefit of TIGIT inhibitors in any solid tumors. For example, there were negative trials in melanoma, gynecological cancer, and lung cancer. The lung cancer trial showed a borderline benefit of TIGIT inhibition, especially in the PD-L1–positive population.

Although all trials [with TIGIT inhibition] have been negative, there [are opportunities to use TIGIT inhibitors with] different modes of action, especially [regarding] the Fc portion. Previously reported phase 3 trials have almost always applied Fc-maintained or Fc-activated TIGIT inhibitors. STAR-221 is the first study to test an Fc-silent anti-TIGIT antibody. [Therefore], we may observe a difference [in outcomes from this trial] compared with previous negative trials.

How might positive results from STAR-221 affect the development of domvanalimab and the placement of the investigational combination among current chemoimmunotherapy regimens for gastric cancers?

It should depend on the result. If [domvanalimab/zimberelimab/chemotherapy] shows an OS benefit compared with chemotherapy plus nivolumab, it should be at least the standard in some populations. However, this depends on the subgroup analysis [where patients are stratified] by PD-L1 status. If it only shows a benefit in the PD-L1–high population, it should be the treatment used for that population [only].

However, if [the combination] shows an [OS] benefit regardless of PD-L1 status, this is also attractive, because usually patients with low PD-L1 status achieve limited benefit with chemotherapy plus a PD-[L]1 inhibitor. If this trial turns out to be positive, why not test this agent in other types of tumors [beyond those] where previous anti-TIGIT therapy failed to show a survival benefit? It should be interesting.

Chemotherapy/nivolumab is standard, especially for patients with a PD-L1 CPS of 1 or higher. [In patients with a] CPS less than 1, [this combination] didn’t show benefit, but there’s no detrimental effect. The [STAR-221] trial was started before the FDA’s Oncologic Drugs Advisory Committee meeting about the restriction of [frontline PD-1 inhibitors to patients with HER2-negative, microsatellite-stable gastric/GEJ adenocarcinoma with a PD-L1 CPS greater than 1]. I don’t expect any large barriers or any differences in this [trial] population compared with the general gastric cancer population regarding CPS frequency.

Additionally, the main objective in this study is to see the treatment effect, especially in patients with a CPS or a TAP score of 5% or higher. [CPS] is being monitored during the trial. It does not seem different from the usual frequency [seen in this population], but the exact results should be reported after the analysis.

References

1. A clinical trial of a new combination treatment, domvanalimab and zimberelimab, plus chemotherapy, for people with an upper gastrointestinal tract cancer that cannot be removed with surgery that has spread to other parts of the body (STAR-221). ClinicalTrials.gov. Updated June 26, 2025. Accessed June 30, 2025. https://www.clinicaltrials.gov/study/NCT05568095
2. Janjigian Y, Oh D, Pelster M, et al. Updates on abstract 433248: EDGE-Gastric arm a1: phase 2 study of domvanalimab, zimberelimab, and FOLFOX in first-line (1l) advanced gastroesophageal cancer. Presented at: 2024 ASCO Annual Meeting. May 31-June 4, 2024. Chicago, IL.

V116, a 21-valent, adult-specific pneumococcal conjugate vaccine (PCV21; Merck) indicated for protection against pneumonia and invasive pneumococcal disease (IPD), was found to exhibit consistent immunogenicity and safety profiles across 3 different manufacturing lots, according to investigators of a study published in Med.¹

Importance of Vaccine Lot Consistency

Ensuring that vaccine efficacy, potency, and safety are consistent across manufacturing lots is critical. Vaccine production is a complex process that can occur over multiple sites and involve numerous stakeholders, with myriad opportunities for mistakes that could impact the health of patients. Investigators say that even subtle changes in the production process can alter the purity, efficacy, or safety of a vaccine lot. These risks are compounded with ever-present barriers in procuring necessary supplies for vaccines and navigating shortages.²

“This compounded risk of biological and physical variability makes vaccine manufacturing more challenging than typical small molecule pharmaceuticals and is a primary root cause of the high proportion of vaccine manufacturing failures and supply shortages,” the authors of a review of the vaccine manufacturing process published in Vaccine wrote.²

Vaccines to protect against Streptococcus pneumoniae (S. pneumoniae) infection, which can lead to community-acquired pneumonia and IPD, have been increasingly manufactured and proliferated across the globe. These conditions lead to significant morbidity and mortality, especially among older adults and those with risk factors that would cause severe disease. Several vaccines targeting S pneumoniae have been developed, most prominently PCVs, which target multiple pneumococcal-causing serotypes that circulate in the community.^1,3

V116 (PCV21) was approved by the FDA in 2024 for the prevention of invasive disease and pneumonia caused by S pneumoniae for patients aged 18 years and older. According to a series of clinical trial data from the STRIDE family of trials, V116 was found to elicit higher immune responses than a comparator vaccine for serotypes unique to V116. Furthermore, the Advisory Committee on Immunization Practices (ACIP) has recommended that adults 65 years and older who had not previously received a pneumococcal vaccine and those 16 to 64 years with known risk factors receive PCV21.^3,4

V116 is Similarly Efficacious Across Vaccine Lots

Although the efficacy of V116 has been proven, the lot consistency of V116—how similar the potency and efficacy of the vaccine is across manufacturing lots—has yet to be determined. These insights could serve as critical indications of the strength of V116’s manufacturing process and identify areas where refinements to the process are necessary. Therefore, investigators of a global phase 3 trial (STRIDE-4; NCT05464420) sought to evaluate the manufacturing consistency of V116.¹

Participants were randomly assigned to receive a single dose of V116 from 1 of 3 lots or the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Thirty days post-vaccination, investigators associated geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) for patients. In addition, systemic and injection-site adverse events (AEs) were examined for 5 days postvaccination, according to the investigators.¹

Results from the analysis indicate that all 3 lots of V116 met equivalence criteria based on GMTs for all 21 serotypes included in the vaccine. GMTs and GMCs were found to be comparable between the combined V116 lots and PPSV23 for shared serotypes and were higher in the combined V116 lots for serotypes unique to V116, reaffirming the superior efficacy of V116 versus PPSV23. Importantly, the AE profiles were similar across the 3 V116 lots, and between the combined V116 lots and PPSV23, the study authors found.¹

Ultimately, these results both reinforce the strong protection provided against S pneumoniae from V116 and solidify the consistent safety and efficacy across vaccine lots of V116. Recipients of V116 can be assured that there are no significant differences between their vaccine and another, with the same protection provided regardless of lot. Pharmacists can discuss a typical vaccine manufacturing process with their patients to address any lingering concerns regarding safety and efficacy.¹

REFERENCES

1. Scott P, Ukkonen B, Caraco Y, et al. A phase 3, randomized trial to evaluate lot-to-lot consistency of V116, an adult-specific pneumococcal conjugate vaccine (STRIDE-4). Med. 2025;100748. doi:10.1016/j.medj.2025.100748

2. Plotkin S, Robinson JM, Cunningham G, Iqbal R, Larsen S. The complexity and cost of vaccine manufacturing—An overview. Vaccine. 2017;35(33):4064-4071.

3. Halpern L. Pneumococcal 21-valent conjugate vaccine generates positive response in adults at increased risk of disease. Pharmacy Times. Published October 21, 2024. Accessed June 30, 2025. https://www.pharmacytimes.com/view/pneumococcal-21-valent-conjugate-vaccine-generates-positive-response-in-adults-at-increased-risk-of-disease

4. Gallagher A. FDA approves V116 for prevention of invasive pneumococcal disease and pneumonia. Pharmacy Times. Published June 18, 2024. Accessed June 30, 2025. https://www.pharmacytimes.com/view/fda-approves-v116-for-prevention-of-invasive-pneumococcal-disease-and-pneumonia

Every protein in the body is encased in a water shell that directs protein structure, provides vital stability and steers function. Because of this, water molecules represent a powerful but largely underappreciated foothold in drug binding studies. Yet structural data about these water networks, usually collected at freezing temperatures, often carry temperature-based structural artifacts. St. Jude Children’s Research Hospital scientists have unveiled a new computational tool called ColdBrew to address this problem. The tool leverages data on extensive protein water networks to predict the likelihood of water molecule positions within experimental protein structures, potentially aiding drug discovery efforts. ColdBrewwas published today in Nature Methods.

Proteins have evolved to fold precisely according to the repulsion and attraction of their amino acid building blocks to water. Water is also key to their activity since it helps guide other molecules, including drug molecules, to bind effectively. Drug discovery efforts based on protein structures use techniques such as X-ray crystallography and cryo-electron microscopy, but these techniques use freezing, or “cryogenic” temperatures, which can distort how water molecules appear. Marcus Fischer, PhD, St. Jude Department of Chemical Biology & Therapeutics, recognized this as a missed opportunity. 

Water molecules in protein structures have so many degrees of freedom that drug discoverers typically throw them out. They’re kind of inconvenient.”

Marcus Fischer, PhD, St. Jude Department of Chemical Biology & Therapeutics, corresponding author on the study

With ColdBrew, seeing is believing

To put this lost information to work, Fischer and first author Justin Seffernick, PhD, St. Jude Department of Chemical Biology & Therapeutics, developed ColdBrew. “Our goal was to make a tool that’s easy to use and understand,” said Seffernick. “For each water molecule, our method can tell us how likely water is to be present at higher temperatures. We also found that this same metric can give us clues about how ligands bind to proteins.”

This is particularly important to drug discovery. “When ligands bind to proteins, they kick out water from binding sites, so we need to pay attention to them in ligand design,” said Fischer. “Encouragingly, we’ve seen in our data that our predictions were best within these binding sites and around ligands.” 

Considering that cryogenic structure-solving techniques can artificially increase the number of water molecules present in a structure, a tool such as ColdBrew can assure researchers that seeing is believing. To this end, Fischer and Seffernick have amassed and made publicly available a comprehensive library based on ColdBrew calculations. 

“To enable the wide use of ColdBrew, we performed calculations on every structure that fit our criteria in the entire Protein Data Bank. We have over 100,000 predictions, which is over 46 million water molecules,” Fischer said. “Remarkably, our results show that drug designers unknowingly avoid tightly bound waters, so actually knowing which ones to avoid could guide the process.”

Authors and funding

The study was supported by grants from the National Institutes of Health (R35GM142772) and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude.

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Blood plasma can harbor DNA changes that could flag cancer years before existing diagnostic tests, an early study hints.

The recent study, published May 22 in the journal Cancer Discovery, found traces of free-floating DNA from dead precancerous or cancerous cells in plasma that had been donated three years before a diagnosis.

LA JOLLA, CA, & PITTSBURGH, PA—New research from the University of Pittsburgh School of Medicine and La Jolla Institute for Immunology, published today in Nature Microbiology, reveals an opportunity for developing a therapy against cytomegalovirus (CMV), the leading infectious cause of birth defects in the United States.

Researchers discovered a previously unappreciated mechanism by which CMV, a herpes virus that infects the majority of the world’s adult population, enters cells that line the blood vessels and contributes to vascular disease. In addition to using molecular machinery that is shared by all herpes viruses, CMV employs another molecular “key” that allows the virus to sneak through a side door and evade the body’s natural immune defenses.

The finding might explain why efforts to develop prophylactic treatments against CMV have, so far, been unsuccessful. This research also highlights a new potential avenue for the development of future antiviral drugs and suggests that other viruses of the herpes family, such as Epstein-Barr and varicella-zoster virus (which causes chickenpox and shingles), could use similar molecular structures to spread from one infected cell to the next while avoiding immune detection.

“If we don’t know what weapons the enemy is using, it is hard to protect against it,” said senior author Jeremy Kamil, Ph.D., associate professor of microbiology and molecular genetics at Pitt. “We found a missing puzzle piece that represents one possible reason why immunization efforts against CMV have been unsuccessful.”

In the United States, approximately one in every 200 babies is born with congenital CMV infection. Of the babies infected, one in five will have birth defects, such as hearing loss, or go on to have long-term health challenges. For most adults, CMV infections are asymptomatic. But a CMV infection during pregnancy presents significant health risks to the developing child and could be deadly for people who are immunosuppressed, including organ transplant recipients.

Because of the large size of its genome and its complicated molecular machinery, CMV long evaded attempts to develop prophylactic treatments. Similar to other herpes viruses, CMV relies on a protein called gH to enter cells of the vessel lining. But unlike other herpes viruses, which use a protein partner called gL to facilitate infection, the new study found that CMV replaces gL with another partner called UL116 and recruits a protein called UL141. The resulting complex of gH-UL116-UL141, called GATE by the authors, then becomes an alternative tool for breaking into cells lining the blood vessels and causing internal damage while simultaneously preventing the body’s own immune system from recognizing the signs of infection.

The newly discovered GATE could become a potential vaccine target for CMV and other herpes viruses.

“Previous attempts to generate a CMV vaccine have failed, but that was before we identified the GATE complex. We hope that new strategies targeting GATE will improve our chances to combat CMV infection, and also perhaps cleanse our bodies of this lifelong infection,” said Chris Benedict, Ph.D., Associate Professor at La Jolla Institute for Immunology and co-senior author of the study with Kamil and LJI Professor, President & CEO Erica Ollmann Saphire, Ph.D., MBA. “If we can develop antiviral drugs or vaccines that inhibit CMV entry, this will allow us to combat the many diseases this virus causes in developing babies and immune-compromised people.”

Other authors of the study, “The GATE glycoprotein complex enhances human cytomegalovirus entry in endothelial cells,” are Michael Norris, Ph.D., of the University of Toronto; Lauren Henderson, Mohammed Siddiquey, Ph.D., both of Louisiana State University Health Shreveport; and Jieyun Yin, Ph.D., Kwangsun Yoo, Ph.D., Simon Brunel, Ph.D., and Michael Mor, Ph.D., all of La Jolla Institute for Immunology.

This research was supported by the National Institutes of Health (grants AI11685, AI139749, AI101423 and T32HL155022) and by ARPA-H APECx contract 1AY1AX000055.

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About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top recipients of funding from the National Institutes of Health since 1998. In rankings released by the National Science Foundation, Pitt is in the upper echelon of all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

A three-dimensional model of lung tissue developed by University of Colorado Cancer Center member Chelsea Magin, PhD, will help the U.S. military better research, treat and prevent lung cancer.

“Military service members are more likely to develop lung cancer than the general population due to a combination of occupational exposures and lifestyle factors,” Magin explains. “Many veterans were exposed to hazardous substances, such as particulate matter from burn pits or diesel exhaust, during military service. Additionally, smoking rates among veterans are approximately twice as high as the general population. Due to these factors, nearly 1 million veterans remain at high risk for lung cancer.”

A three-dimensional model of lung tissue developed by CU Cancer Center member Chelsea Magin, PhD, will help the U.S. military better research, treat, and prevent lung cancer

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— CU Cancer Center (@cucancercenter.bsky.social) June 26, 2025 at 2:02 PM

Cancer in three dimensions

In response to a call for novel research on lung cancer treatment and prevention, Magin recently received a Department of Defense (DoD) grant for her 3D hydrogel lung modeling system, which she says is superior to the petri dish cultures commonly used to study lung cancer cells.

“Our research uses hydrogel materials that contain proteins from the lungs,” says Magin, principal investigator of the Bio-Inspired Pulmonary Engineering Laboratory in the Department of Bioengineering at the CU School of Medicine. “We want to compare healthy lungs, lungs from people who smoke, and lungs from lung cancer patients. We can put those proteins into our material, then put our material around a very thin slice of lung tissue that has all the cells and architecture of the lung. We can use that model to look at how the different proteins in the lungs influence the initiation of lung cancer.”

Collaborative effort

Magin’s research lab is also working with the lab of CU Cancer Center member Erin Schenk, MD, PhD, to study how different immunotherapy treatments interact with different types of lung tissue. The research also includes collaboration with Bradford Smith, PhD, associate professor of bioengineering, and CU Cancer Center member Robert Keith, MD, professor of pulmonary sciences and critical care medicine.

“The material that holds your cells together is called the extracellular matrix, and it’s made up of proteins and carbohydrates and other big molecules,” says Magin, also an associate professor in the Department of Pediatrics and Division of Pulmonary Sciences and Critical Care Medicine. “We think that different exposures, like being exposed to smoking or not, creates changes in that microenvironment that can influence the initiation of or susceptibility to cancer. It could also influence whether you are a good candidate for immunotherapy treatment.”

Predictive path

Over the course of the three-year project, Magin and her co-researchers plan to analyze the proteins they put into the hydrogels, looking for differing protein signatures in healthy, cancerous and smoke-exposed lungs.

“What we learn about how the tissue responds to each protein signature will help us understand things like, ‘If a patient has this protein signature, they’re more likely to get cancer, or their cancer is more likely to be aggressive,’” Magin says. “We also hope to learn which protein signatures are most responsive to the immunotherapies.”

Eventually, Magin hopes, the research could lead to a clinician’s ability to biopsy a small amount of lung tissue and analyze its protein signature to determine the best course of treatment.

“They could tailor the therapies based on that combination of proteins,” she says.

This article was originally published June 9, 2025, by the University of Colorado Cancer Center. It is republished with permission.

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