Dr Shreenivas on the Association Between MUC1 and CLDN18 in GI Cancers

"We did extensive gene expression profiling, looking at the upregulation and downregulation of pathways, and we found a very strong correlation between MUC1 and CLDN18.”

Aditya Shreenivas, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses findings from a gene expression profiling analysis of the association between Claudin 18 (CLDN18) and MUC1 in gastrointestinal (GI) cancers, and their potential implications for targeted therapy development.

In this multi-institutional study, Shreenivas and colleagues conducted genomic profiling on samplesfrom heterogeneous patient populations across Southern Asia and Europe. These included 651 upper and lower GI cancer samples, 316 pancreaticobiliary cancer samples, and 76 hepatocellular carcinoma samples. 

The study assessed the expression patterns of CLDN18, a tight junction protein, and MUC1, an epithelial biomarker associated with aggressive malignancies. The analysis aimed to determine whether co-expression of these biomarkers could inform novel therapeutic strategies. Potential correlations between CLDN18 expression and established molecular markers, including PD-L1, tumor mutational burden, and HER2, were also evaluated.

the 2025 ASCO Gastrointestinal Cancers Symposium 

demonstrated that Claudin 18 was upregulated in 20% of analyzed samples (n = 321). Among cases with concurrent MUC1 and CLDN18 gene expression data (n = 118), MUC1 overexpression was observed in all CLDN18–positive tumors. However, no statistically significant correlation was identified between CLDN18 and HER2, PD-L1, TMB, or microsatellite instability (MSI), suggesting that CLDN18 may serve as an independent predictive biomarker. Additional genomic analyses revealed frequent gene amplifications in MYC (13%), ERBB2 (5%), and CCND1 (5%). MSI-high cases accounted for 2.4% of the overall cohort.

Shreenivas notes that the spatial reorganization of these biomarkers during malignant transformation may enhance their accessibility to therapeutic agents. CLDN18 has emerged as a viable therapeutic target, as demonstrated by the approval of zolbetuximab, a monoclonal antibody directed against CLDN18. Additionally, other investigational therapies, including antibody-drug conjugates, high-affinity antibodies, and CAR T-cell therapies, are being explored for CLDN18–positive tumors.

Shreenivas highlights the strong correlation between MUC1 and CLDN18 expression, suggesting the potential for dual-targeting approaches in future therapeutic strategies. He emphasizes the need for further validation through immunohistochemical assays and the development of bispecific antibodies capable of targeting both pathways simultaneously. Additionally, future studies will investigate tumor heterogeneity and optimize treatment modalities that account for varying levels of CLDN18 expression.

Shreenivas concludes that these findings underscore the potential role of MUC1 and CLDN18 as complementary biomarkers in GI cancers, highlighting the need for continued research to refine personalized treatment strategies incorporating targeted therapies.

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Aditya Shreenivas, MD, MS, discusses the association between MUC1 and Claudin 18 in GI cancers.

It is difficult to stay up-to-date with the changing treatment paradigm in hematology-oncology. This field is rapidly evolving, and the explosion of information is too much to handle sometimes. Fellows in training are generally expected to stay abreast of current treatment modalities and breakthrough research, but doing so is slowly becoming a challenge for all of us. It is important to note that in 2017, the FDA issued 58 new approval notifications in hematology-oncology, much more than in any other field of medicine.

 According to an estimate from a PubMed search, more than 1.17 million articles have been published in the field of oncology over the past 10 years. Jeremy Warner, MD, MS, published a review in 2015 noting that PubMed contains more than 2.7 million articles filed under the Medical Subject Heading “neoplasms.” He also observed that the number of articles published in oncology was much higher than that of other medical fields like cardiology and endocrinology.

 These observations are a testament to the explosion of data in the field of cancer medicine.

The constant interplay of research between the disciplines of oncology, molecular biology, genetics, and bioinformatics have made this a complicated field. Although medical research data are now readily available online to both physicians and patients, it is often a challenge to glean relevant information from them. As physicians, it is very important for us to develop skills to determine what is important in the context of clinical care. It is also essential for us to pay adequate attention to rapidly evolving guidelines in oncology for the benefit of our patients. But this is a Herculean task.

There are several ways to tackle the problem of information overload. I think the most important way to stay up-to-date is to develop a habit of continuous learning. We should make every effort to block out a specific time each day to catch up on reading, even if it’s just 30 to 45 minutes. For trainees, I believe reading about different topics each day or the literature around a case presented in clinic would be ideal.

We should also take a cue from lawyers—unbelievable, I know. A lawyer friend told me that group discussions are a common practice in law school and are quite helpful in preparing students for tough internal examinations. Group discussions are a great way of improving understanding of a subject. It also helps us identify our shortcomings and weaknesses in a short span of time. Routine peer-to-peer interaction can be a useful way of staying abreast of changing guidelines and cutting-edge research.

If you ask senior oncologists, they will probably tell you to read top peer-reviewed journals, such as the 

 to stay current in hematology-oncology. Although there is no question about the accuracy and quality of data available in these journals, it is a challenge to follow all the relevant information on different disease subtypes. Hence, it is important to carefully choose and pay attention to landmark studies that have led to new drug approvals or are changing treatment strategies.

 is another easy way of keeping informed if you don’t always have the time to read journals. National meetings like those hosted by the American Society of Clinical Oncology, the American Society of Hematology, and the American Society of Blood and Marrow Transplantation are an important source of updated information for most of us. These meetings give us an opportunity to interact with experts and obtain firsthand information about breakthrough research in our field. Prioritize listening to the keynote presentations if your time is limited at these meetings. These presentations are practice changing, and their findings are fair game for future board examinations. Board review lectures are also a great resource and highlight the most recent and clinically relevant data.

Another way to stay up-to-date is by creating email notifications on PubMed for topics of interest so that every time a new article on a specified topic is published, an email notification will be sent to your inbox, and you can quickly read the article on your mobile device.

Hematology-oncology fellows, unlike their counterparts in cardiology, nephrology, rheumatology, and endocrinology, have to pass 2 boards after graduating, which adds more stress to their lives post fellowship. According to the American Board of Internal Medicine’s 5-year report of first-time test takers, the average board passing rate for hematology has been one of the worst among all specialties of medicine.

 Although board pass percentages have started to improve, it will be interesting to see whether the trend continues.

Not to sound cynical, but there can be only 2 explanations for this trend: Either test takers are becoming smarter or the test itself is becoming easier. Honestly, I feel we are better prepared for these examinations than our predecessors because of increased awareness and easy access to board review materials these days. I guess it’s also reasonable for some of us to schedule these examinations at our convenience and not take both boards in the same year if we feel that our preparation is suboptimal. Fellows should also take in-training examinations very seriously. These may help us identify areas that need our special attention and time. Results from some studies have also shown that they remain a great predictor of hematology-oncology certification examination scores and are probably more accurate than a program director’s assessment of our medical knowledge.

The incorporation of medical decision-making tools and computer applications into clinical practices has signaled a major revolution in medicine. Oncologists already use mobile apps like the National Comprehensive Cancer Network Guidelines App, UpToDate, and Medscape as convenient sources of information and to streamline treatment algorithms of disease subtypes. Mobile apps and clinical vignette modules can also be upgraded to take advantage of better graphics and animations, to enhance physician engagement with their patients, and to make learning more fun. Animation-enhanced learning can be introduced to educate physicians about specific diagnostic, treatment, and follow-up scenarios. All these ideas, if implemented in a better way, could benefit all of us.

There is an urgent need to develop better learning tools for trainees to not only stay up-to-date but to also excel in this field. As future hematologist-oncologists, we are obligated to provide the best care possible to our patients and stay informed.

Hematology/oncology (cancer) approvals & safety notifications. FDA website. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm. Updated June 20, 2018. Accessed July 24, 2018.

Warner JL. Grappling with the data explosion in oncology. 

 2015;11(2):102-103. doi: 10.17925/OHR.2015.11.02.102.

First-time taker pass rates - initial certification. American Board of Internal Medicine website. Accessed July 24, 2018. abim.org/~/media/ABIM%20Public/Files/pdf/statistics-data/certification-pass-rates.

Collichio FA, Hess BJ, Muchmore EA, et al. Medical knowledge assessment by hematology and medical oncology in-training examinations are better than program director assessments at predicting subspecialty certification examination performance.

 2017;32(3):647-654. doi: 10.1007/s13187-016-0993-6.

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Aditya V. Shreenivas, MD, MSCR, says a habit of continuous learning is the ideal way to stay informed about the latest data.

Aditya V. Shreenivas, MD, MSCR

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