Ashling Wahner joined MJH Life Sciences in 2022. She produces 

, and helps ensure timely publication of news content and announcements from the FDA approval pipeline. She also attends conferences live and virtually to conduct video interviews and produce written coverage. Email: awahner@mjhlifesciences.com

AMB-05X in ctDNA+ CRC. | Image Credit: © Anatomy Insider - stock.adobe.com

Detectable circulating tumor DNA (ctDNA) is a surrogate marker for the presence of minimal residual disease (MRD). It is associated with an increased risk of disease recurrence after curative-intent therapy in patients with colorectal cancer (CRC).

 However, the optimal treatment for patients with detectable ctDNA without measurable radiographic disease after completion of standard-of-care (SOC) therapy has yet to be determined. A phase 2 study is seeking to expand this treatment paradigm by investigating the colony-stimulating factor 1 receptor (CSF1R)-directed antibody AMB-05X in patients with ctDNA-positive CRC.

What was the rationale for investigating AMB-05X in patients with CRC with detectable ctDNA?

Previously, researchers at The University of Texas MD Anderson Cancer Center in Houston identified the presence of CSF1R-positive, pro-oncogenic macrophages in murine models with CRC micrometastases. In vivo, blocking CSF1R with an anti-CSF1R antibody was shown to reduce levels of pro-tumorigenic micrometastases and CD163-positive macrophages in mice with MRD, as well as prevent the development of CRC macrometastases.

What is the design of the phase 2 trial evaluating AMB-05X in ctDNA-positive CRC?

This investigator-initiated, prospective, single-arm, open-label phase 2 trial (NCT06617858) is enrolling patients aged at least 18 years with histologically or pathologically confirmed adenocarcinoma of the colon or rectum 

 Patients must have completed all planned curative-intent therapy, including chemotherapy and surgery, if indicated, for stage I to IV CRC that has resulted in no evidence of measurable radiographic disease per RECIST 1.1 criteria and/or clinically detectable disease at least 28 days after completion of planned SOC treatment.

 Patients are also required to have a positive ctDNA assay at least 28 days after completing planned SOC treatment, adequate organ and marrow function, and an ECOG performance status of 0 or 1.

Patients will be excluded if they have or have had a prior or concurrent malignancy within 3 years of trial registration for which the natural history of treatment may interfere with the safety or efficacy assessment of AMB-05X or which requires concurrent therapy; clinically significant hepatobiliary disease that would lead to excessive treatment risk during the study; significant concomitant health conditions; persistent adverse effects related to prior anticancer therapy that are at least grade 2 in severity; and a coexisting separate disease, metabolic disorder, clinically significant laboratory result, or any other condition that may prohibit the use of AMB-05X or put the patient at undue risk of harm.

Patients in this single-arm trial will receive AMB-05X at a dose of 15 mg/kg intravenously every 2 weeks for a maximum of 6 months.

 Following treatment, patients will undergo postintervention assessments and surveillance; this includes blood collection for ctDNA analysis and radiographic assessments (CT or MRI) conducted every 3 months (± 14 days). The trial plans to enroll a total of 15 patients. As of October 7, 2025, 10 patients had been dosed.

The primary end point is the identification of the ctDNA clearance rate at the time of completing therapy with AMB-05X. Exploratory end points include the estimated 2-year disease-free survival and overall survival rates; the pharmacokinetic profile of AMB-05X; correlations between ctDNA changes and clinical outcomes; and the association between clinical outcomes and pharmacokinetic, pharmacodynamic, and additional biomarker changes.

The trial was initiated on December 4, 2024, and is being conducted at The University of Texas MD Anderson Cancer Center.

 The estimated primary completion date is February 1, 2026, and the trial is expected to run until February 1, 2028. The trial is currently enrolling.

LaPelusa M, Mohamed A, Sun R, et al. Open-label phase II trial of AMB-05X for patients with ctDNA(+) colorectal cancer after curative-intent treatment. 

. 2025;36(suppl 2):S593-S594. doi:10.1016/j.annonc.2025.08.1478

Trial of AMB-05X for patients with ctDNA(+) colorectal cancer after curative-intent treatment. ClinicalTrials.gov. Updated October 30, 2025. Accessed November 4, 2025. https://clinicaltrials.gov/study/NCT06617858

Articles

Detectable circulating tumor DNA (ctDNA) serves as a surrogate marker for minimal residual disease (MRD) in colorectal cancer (CRC) and indicates a higher risk of recurrence post-curative therapy. A phase 2 trial is exploring the CSF1R-directed antibody AMB-05X in ctDNA-positive CRC patients. The trial, initiated at MD Anderson Cancer Center, involves patients with no measurable radiographic disease post-standard therapy. The primary endpoint is ctDNA clearance rate, with exploratory endpoints including survival rates and pharmacokinetic profiles. The trial began in December 2024 and is expected to complete in February 2028.

A phase 2 study is using ctDNA positivity to select patients with CRC who may benefit from treatment with the CSF1R-directed antibody AMB-05X.

CSF1R Blockade With AMB-05X May Improve Tumor Control in ctDNA+ CRC

Jax DiEugenio joined MJH Life Sciences in 2024, first as an editorial intern before transitioning into a full-time assistant editor for 

. A recent College of New Jersey graduate, Jax majored in Journalism/ Professional Writing with minors in Public Health and Anthropology. He is also pursuing a Master's Degree in Public Health, concentrating on health communications.

The FDA approval of zongertinib (Hernexeos) has introduced a novel, precision-targeted treatment approach for patients with 

-mutant non–small cell lung cancer (NSCLC), a biologically aggressive subtype often associated with high rates of central nervous system (CNS) metastases and limited response to immunotherapy, according to Martin Dietrich, MD, PhD.

-mutant NSCLC shares key molecular features with 

-driven disease, including low immunogenicity and poor responsiveness to checkpoint inhibitors, leaving chemotherapy as the historical mainstay of treatment. 

On August 8, 2025, the FDA approved zongertinib

 a highly selective HER2 tyrosine kinase inhibitor (TKI), based on data from the phase 1/2 Beamion LUNG-1 study (NCT04886804), which was designed to address this significant unmet need.

On August 8, 2025, the FDA approved zongertinib, the first precision-targeted HER2-directed therapy for patients with 

In the Beamion LUNG-1 trial, zongertinib achieved ORRs of 75% and 44% in chemotherapy-pretreated and HER2-ADC–exposed cohorts of patients, respectively.

The agent showed strong intracranial activity, durable responses, and a favorable safety profile, with further evaluation ongoing in the Beamion LUNG-2 trial.

Evaluable patients who had received prior platinum-based chemotherapy and had not been previously treated with a HER2-targeted TKI or antibody-drug conjugate (ADC; n = 71) achieved an overall response rate (ORR) of 75% (95% CI, 63%-83%); 58% of patients achieved a duration of response (DOR) lasting at least 6 months.

 Among those who had received both platinum-based chemotherapy and a prior HER2-targeted ADC (n = 34), the ORR was 44% (95% CI, 29%-61%), and 27% of patients achieved a DOR lasting at least 6 months.

, Dietrich expanded on the meaningful clinical activity observed with zongertinib in both treatment-naive and previously treated patients with 

-mutant NSCLC, highlighting the agent’s strong intracranial efficacy, durable responses, and favorable safety profile. He also discussed how these findings could support integrating zongertinib as a targeted option earlier in the treatment sequence—a question being addressed in the ongoing phase 3 Beamion LUNG-2 trial (NCT06151574), which aims to further define the agent’s role within HER2-directed treatment paradigms.

Dietrich currently serves as a medical oncologist with The US Oncology Network Cancer Care Centers of Brevard, practicing in Rockledge, Florida. He is also an assistant professor of internal medicine at the University of Central Florida in Orlando.

: What is the significance of the FDA approval of zongertinib within the current context of the 

-mutant NSCLC is one of the most aggressive and brain-metastatic subsets of lung cancer, and it is difficult to treat. It shares several biological features with 

-mutated disease, so we see limited efficacy with immunotherapies. The datasets are small, but what we know so far is that immunotherapy [in 

-mutant disease] seems to produce response rates similar to [those in] 

-[mutant disease, which are] low. We’re mainly dependent on chemotherapy in this context, so introducing the first targeted therapy, [zongertinib], for 

The Beamion LUNG-1 study evaluated zongertinib at 120 mg daily in a multi-cohort design.

 In cohort 1—the most relevant group, which included patients with tyrosine kinase domain [TKD] mutations, the most common subtype—the ORR was 75%.

 We’ve seen strong correlations [between this agent and] intracranial response in other datasets, and the durability [of response] was good. Adjusted for underlying genetic background, the median DOR and estimated progression-free survival were both well above 1 year, which is encouraging in a pretreated subset.

What did Beamion LUNG-1 reveal about the efficacy of zongertinib across patient subsets?

In other cohorts, such as cohort 3 and cohort 5, responses were observed in patients with non-TKD mutations and in those previously treated with fam-trastuzumab deruxtecan-nxki [Enhertu], with response rates of approximately 30% to 40%. This provides proof of concept that these patients can benefit from targeted therapy. Ideally, we want to offer targeted agents as early as possible, given their [association with] improved quality of life, strong efficacy, and favorable safety profiles.

What characteristics distinguish zongertinib from other HER2-targeted therapies evaluated to date?

[Zongertinib] is the first HER2-targeted therapy that effectively captures the most common exon 20 insertion mutations in 

 [with a high degree of specificity] and minimal overlap with EGFR inhibition. [Because of that], we’re not seeing many on-target adverse effects in the skin or gastrointestinal tract, which is positive.

Looking ahead, what are the next steps for evaluating zongertinib for 

These data are currently strongest for the second line and beyond, [where zongertinib is currently] approved. [However,] the ongoing Beamion LUNG-2 trial will serve as a confirmatory study, comparing the phase 3 KEYNOTE-189 trial [NCT02578680] regimen [of pembrolizumab (Keytruda) plus chemotherapy] against zongertinib in the first-line setting.

I’m not overly enthusiastic about that trial because the platinum/pemetrexed/pembrolizumab control arm hasn’t been validated in the 

-mutant subset. [That study] is more of an extrapolation from the broader adenocarcinoma paradigm. Still, we’ll have to see how the FDA decides, how guidelines [evolve], and how [insurance providers] will implement [coverage for] the drug. Overall, it’s exciting to finally have a HER2-targeted agent that delivers high efficacy, CNS activity, and a favorable safety profile.

FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed October 31, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations

Hernexeos. Prescribing information. Boehringer Ingelheim; revised August 2025. Accessed October 31, 2025. https://patient.boehringer-ingelheim.com/us/products/hernexeos/bipdf/hernexeos-dtc-prescribing-information

Martin Dietrich, MD, PhD, discusses how zongertinib offers a new targeted option for HER2-mutant NSCLC, yielding durable responses and strong CNS activity.

FDA Approval of Zongertinib Marks a Targeted Advancement for Patients With HER2-Mutant NSCLC

Maurie Markman, MD, is president of Medicine & Science at City of Hope Atlanta, Chicago, and Phoenix

Having grown up in the cradle of academic medicine, writing this commentary gives me no pleasure. Unfortunately, the rapidly increasing dysfunction associated with what has reasonably been considered the coin of the realm for countless decades, the publication of original research or regularly cited review articles in high-impact 

The current state of affairs is not the result of a single event and did not achieve its dreary state over a short period. However, it is no longer deniable that there has been a palpable acceleration in the magnitude and negative effects of this dysfunction, which, of course, raises serious concerns.

This discussion begins by highlighting a recent report from Australian investigators who employed a machine learning model to examine the oncology literature from 1999 to 2024 for the presence of peer-reviewed publications that possessed the hallmarks of being produced in fraudulent paper mills.

Distressingly, the effort identified 9.87% of the entire literature as falling into this category, with an increasing percentage of published manuscripts identified as fraudulent in the most recent years included in the analysis. To some observers, perhaps the most surprising finding was that a similar percentage of paper mill manuscripts were found in the “top 10% of journals by impact factor.” Finally, and remarkably, “over 170,000 papers by authors from Chinese institutions were flagged” in this paper mill model.

To be clear, the identification of manuscripts as possibly originating from paper mills through this model does not prove this accusation. However, the magnitude of the observations, as well as evidence of an increase in the percentage of papers that fall into this category over the past several decades, must be considered a matter of great concern.

A second report highlights an additional worrying trend: fake reviewers are being selected for fraudulent manuscripts.

 This analysis revealed a particularly unique problem. Once individuals are identified as authors of peer-reviewed manuscripts, regardless of the ultimate scientific validity of the papers or even the existence of these individuals, they are subsequently more likely to be asked to serve as peer reviewers. When new manuscripts are submitted from these paper mill organizations, the authors may “suggest” specific individuals as potential “reviewers” for their papers who have been programmed to submit favorable reviews. While clearly complex, this scenario provides evidence for the sophistication and coordination of the groups responsible for this rapidly expanding paper mill enterprise.

In summary, the scientific publication peer-review process is on an increasingly unstable footing. While the academic leadership, scientific journal publishers, and institutions that are most frequently responsible for paying the bills (eg, governmental agencies and universities) discuss the future of this vital operation, the situation worsens.

Two fundamental components of the peer-review process––trust and the willingness of the broad scientific community (including, in the case of medical sciences, active clinicians and investigators) to willingly volunteer their time and expertise to ensure as much as humanly possible the existence and continuation of a highly robust peer-reviewed literature––are under active challenge.

In an earlier era, and speaking specifically about clinical medicine, there were far fewer peer-reviewed journals, both general medical and specialty-focused publications. A request from the editor of one of these journals was likely met with at least modest enthusiasm (always appreciating the question of individual time management), a recognition that the requestor (or someone within the journal staff) appreciated that those asked to provide a peer review had achieved a sufficient level of expertise that is required to participate in this critical process.

) that those who examined submitted reviews would, at some level, evaluate the quality, completeness, and effort that went into this exercise. One might have considered it an honor (and that likely remains the case for many scientific publications) to have been asked. This would be particularly relevant for a more junior faculty member or academically inclined clinician.

However, today, with the virtual explosion in the number of claimed “peer-reviewed scientific journals,” with many recognized as being nothing more than a shady business venture (“predatory journals”),

 it is often difficult for an individual asked to provide a peer review to know if the request is coming from a legitimate entity. And, of course, as noted above, the request to review comes without compensation, even though it is well recognized that individuals and organizations profit from this publication venue.

Further, because of the ever-increasing specialization and complexity inherent within basic and translational laboratory science and clinical medicine, the requirements associated with providing an objectively meaningful peer review only magnify. Team science, both in the clinical and nonclinical domains, the uniqueness and nuances of specific research efforts, and the requirement for complex statistical analysis only intensify questions about the adequacy of the peer-review process. One might reasonably inquire how one or even several peer reviewers are able to adequately evaluate the reported science contained within a manuscript that includes several dozen or even more than 100 authors.

Publishers are clearly attempting to deal with the rapidly evolving situation, including strategies designed to limit the widespread use of large public databases, a common strategy of paper mills to create meaningless but “statistically significant” observations with the specific purpose of adding the names of individuals willing to pay to play to achieve authorship status.

 Unfortunately, well-intended strategies designed to improve the availability of scientific publications have inadvertently added to the problem, for who would likely be in the best position to have the funds necessary in this “open access” arrangement: individual researchers, a university struggling to sustain its operations, or a pay-to-play paper mill? Of course, the answer here is painful, but obvious. 

Finally, it is critical to acknowledge the role of artificial intelligence (AI) in both accelerating the problem and providing at least one critical component of a solution. The widespread availability of AI tools has dramatically increased the opportunity for paper mills and other malicious strategies to create and submit fraudulent science and (as noted above) negatively affect the essential peer-review process.

However, one might hope that in the future the large community of organizations and individuals deeply invested in ensuring the future of the scientific communication process (eg, academics, publishers, governmental regulators, and patient advocates) will see a way to work together and effectively employ tools such as AI with the plan to develop, pilot, and subsequently embrace approaches that maintain and enhance its essential objectivity and quality.

Scancar B, Byrne JA, Causeur D, Barnett AG. Revealing the paper mill iceberg: AI-based screening of cancer research publications. 

. Preprint posted online September 3, 2025. doi:10.1101/2025.08.29.673016

Naddaf M. Journals infiltrated with 'copycat' papers that can be written by AI. 

. Published online September 23, 2025. doi:10.1038/d41586-025-03046-z

Leung JG, Wieruszewski PM, Stee L, Takala CR, Palmer BA. Predatory journals: a cautionary tale and a lesson in copyright transfer. 

. 2020;95(3):441-444. doi:10.1016/j.mayocp.2019.09.001

Ohlert T, Smith MD, Collins SL, et al. Drought intensity and duration interact to magnify losses in primary productivity. 

. 2025;390(6770):284-289. doi:10.1126/science.ads8144

O’Grady C. Papers based on open health data face bans. 

. 2025;390(6770):222-223. doi:10.1126/science.aed1020open_in_new

Concerns Escalate About the Fundamental Integrity of Scientific Peer-Reviewed Literature

The non–small cell lung cancer (NSCLC) treatment paradigm has welcomed the addition of numerous targeted therapies over the past several years, prompting a complementary increase in molecular testing rates and innovative tumor sequencing methods. However, persisting barriers to testing, such as tissue insufficiency, emphasize the need for increased diligence through repeat biopsies and improved testing alternatives such as liquid biopsies, according to lung cancer experts interviewed by 

“[Now] couldn’t be a more important time to do biomarker testing in patients with lung cancer,” Benjamin P. Levy, MD, said.

Levy is the clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital and an associate professor of oncology at Johns Hopkins University School of Medicine in Washington, DC.

What is the prevalence of biomarker testing in NSCLC?

Levy explained that in his practice, it is standard to perform molecular testing in all patients with nonsquamous NSCLC, regardless of stage, as a growing collection of clinical data has demonstrated that those test results are often instrumental in guiding treatment decisions. He noted that historically, testing was not considered mandatory in patients with squamous NSCLC due to a lack of known actionable mutations in that disease subtype. However, he emphasized that more recent research has revealed the presence of targetable mutations in patients with squamous disease. Therefore, the NCCN clinical practice guidelines for the treatment of NSCLC now state that molecular testing for alterations in genes such as 

 should be conducted through broad molecular profiling.

What Types of Molecular Testing Should Be Performed in Patients With NSCLC?

Although DNA-based next-generation sequencing (NGS) has long been the standard platform for biomarker testing, the incorporation of RNA-based testing has risen to the forefront of best practices, according to Levy.

“The world has changed with the detection of fusions, and these fusions are better interrogated and unearthed with RNA-based testing,” Levy said.

Joel Neal, MD, PhD, added that DNA-based testing may not always report the presence of large gene rearrangements, further advocating for the use of RNA-based assays.

Neal is a professor of medicine in the Division of Oncology at the Stanford Cancer Institute at Stanford University in Palo Alto, California.

“RNA-based assays, where we’re looking at the mRNA product that’s already been made by the cells, and then looking at those RNA sequences, are a lot more sensitive for finding 

 [rearrangements], and all other rearrangements, too,” Neal said.

Thusly, obtaining testing results requires the use of a tissue-based platform that analyzes both DNA and RNA, the experts explained.

Beyond NGS, Levy emphasized that patients with advanced-stage disease should also undergo immunohistochemistry testing for PD-L1 expression, HER2 expression, and 

 amplification to determine their eligibility for FDA-approved therapies.

“We're understanding a lot more about NSCLC than we ever did, and [this is] leading toward more effective and more personalized treatments,” Neal noted.

What is the role of liquid biopsy in lung cancer molecular testing?

Tissue-based testing in every patient with NSCLC has and continues to be the gold standard that all oncology practices are recommended to follow, Levy noted. However, the historical reliance on tissue alone has resulted in untested patients due to insufficient tissue quantities and financial barriers, the experts noted. For instance, the retrospective MYLUNG consortium pragmatic study, which evaluated real-world biomarker testing patterns in The US Oncology Network, found that among patients with metastatic NSCLC, although NGS testing rates were low compared with the rates of testing for individual biomarkers, this rate increased from 33% to 45% from 2018 to 2020 (

“Even under the best circumstances, when you get a large piece of tissue, either with a fine-needle aspiration or a core biopsy, there are times where there's just not enough…tissue to allow for appropriate, comprehensive NGS,” Levy explained.

The scenario of inadequate tissue is where the role of blood-based assays play critical importance, Levy said. He explained that in the absence of tissue-based results, plasma genotyping may reveal actionable markers and inform patient care.

Furthermore, Neal noted that liquid biopsy can be a useful tool for verifying biopsy results or performing repeat testing.

“We should be able to believe any positive assay, but in a patient without a smoking history and without another oncogenic driver that we've identified, I'll always go looking more and more,” he said. “[I will] probably do RNA-based testing and tissue-based testing if it hadn't been done before to try to make sure we're not missing something. Because these [targeted therapies] are so effective, we can't afford to have a patient who we don't know we can use them in.” 

However, Neal noted that liquid biopsy assays are sometimes not as sensitive as tissue-based tests, especially when detecting RNA gene rearrangements. Therefore, striving to obtain adequate samples from repeat tissue biopsies should be a priority when enough tissue has not been obtained in the past.

“I have a patient who was treated with chemotherapy and other options for almost 10 years in the metastatic setting, and we kept trying to get more tissue and couldn't,” he said. “Eventually, a couple years ago, a repeat biopsy was able to get enough tissue and found a 

 gene rearrangement. Be persistent [with testing], even if it's many, many years after initial diagnosis.”

What additional barriers to biomarker testing remain for patients with lung cancer?

Although several targeted agents have received FDA approval for select patients with NSCLC who are found to have actionable alterations based on biopsy results, ensuring patient access to testing and therapy at every point in the diagnosis and treatment pathway is crucial, according to Christian Rolfo, MD, PhD. He highlighted that this needs to be a global initiative to ensure testing and therapeutic opportunities are not missed due to financial or regulatory constraints.

Rolfo is the director of the Division of Medical Oncology at The Ohio State University Comprehensive Cancer Center—James and a professor at The Ohio State University College of Medicine in Columbus.

“[As much as we need to] have access to the testing, [we need to] equally have access to the drugs,” Rolfo explained. “In the United States, we are very privileged that we have access to these drugs that are approved by FDA. However, that is not the reality in other countries. [We should be] trying to make these barriers around the globe erased. That is the idea to capture more patients who can get the benefits of these drugs.”

What are best practices for multidisciplinary biomarker testing?

Levy emphasized that implementing and sustaining successful biomarker testing practices at any institution starts with a dedicated “physician champion” who can create institution-wide testing standards and oversee the process from beginning to end.

“Sometimes the test is just not done,” Levy noted. “Oftentimes, it'll sit in pathology or, unfortunately, is just never ordered, either by the medical oncologist or the pathologist. Also, there is a tremendous amount of challenges with coordination and getting those results back. Even when the test is done and it's sent out, having it in the electronic medical record ready to [be used in clinic] can be a challenge.”

Levy’s recommendations for how institutions can bridge these gaps include setting standards for optimal tissue procurement, including communication between medical oncologists and interventional radiologists, interventional pulmonologists, and surgeons about choosing optimal tissue samples in a given patient. From there, institutions should create guidelines for how to act on the results.

How might AI help address barriers to biomarker testing in NSCLC?

As the molecular testing field advances, new technologies may play a role in further personalizing test results and alleviating some of the barriers to more widespread testing practices. For instance, artificial intelligence (AI) stands out as an evolving asset, experts noted.

“AI is pretty unique,” Levy said. “AI, in and of itself, may help us better define the right biomarkers for lung cancer outside of the ones we already have. AI I view as being able to interrogate the tissue in different ways and come up with unique ways to potentially treat it. AI also may help us get answers with smaller amounts of tissue. Maybe tissue insufficiency will get a little better when AI is at play.”

Rolfo also emphasized opportunities for AI use at diagnosis and any other time  when patients undergo biopsies.

“The integration of, for example, digital pathology [may play a role in] distinguishing these patients quickly,” he reported. “There are already several initiatives working in diagnostics…based on simple technologies [that may allow us to] have access [to test results] quickly with a rapid test for treatment [eligibility]. This is speeding up the process…from the diagnosis to the drug that is crucial to get results.”

Levy also foresees a potential role for AI in identifying barriers to molecular testing within individual institutions and streamlining standard operating procedures to mitigate some of the organizational issues that lead to delayed or missed testing opportunities.

Rolfo concluded that although testing barriers remain, improvements in testing strategies and accessibility will continue to move the needle in the development of targeted therapies that may in turn bolster the NSCLC treatment paradigm.

“For a common disease that, some years ago, we were using a few drugs in, we have nowadays a rare [set of] diseases that [represent] a fraction of different tumors, characteristics, and different populations that make this disease much more chronic, [but also] much more easy to treat in these populations,” he said. “[We] hope that in the future, [there is] brilliant research coming [that will] continue this fascinating success we are having with targeted therapies.”

NCCN. Clinical Practice Guidelines in Oncology. Non-small cell lung cancer, version 8.2025. Accessed September 18, 2025. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

Robert NJ, Espirito JL, Chen L, et al. Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network. 

. 2022;166:197-204. doi:10.1016/j.lungcan.2022.03.004

The treatment landscape for non-small cell lung cancer (NSCLC) has evolved with the introduction of targeted therapies, necessitating increased molecular testing and innovative sequencing methods. Despite advancements, challenges such as tissue insufficiency persist, highlighting the importance of repeat biopsies and liquid biopsies. Experts emphasize the need for comprehensive molecular profiling, including both DNA and RNA-based testing, to identify actionable mutations. Liquid biopsies offer a complementary approach, though they may lack sensitivity compared to tissue-based tests. Global access to testing and therapies remains a critical issue, with AI potentially aiding in overcoming barriers.

Lung cancer experts share the evolution of biomarker testing that has led to advances in patient selection for treatment, as well as challenges that future developments may address.

Tracy Ann Politowicz

Articles

CSF1R Blockade With AMB-05X May Improve Tumor Control in ctDNA+ CRC

FDA Approval of Zongertinib Marks a Targeted Advancement for Patients With HER2-Mutant NSCLC

Concerns Escalate About the Fundamental Integrity of Scientific Peer-Reviewed Literature

Targeted Therapies Drive Demand for Comprehensive Biomarker Testing in NSCLC