CD44 is best known as a receptor for hyaluronan, a large sugar-rich molecule found in the extracellular matrix—the structural network that surrounds cells. When hyaluronan binds to CD44, it can activate intracellular signalling pathways that regulate proliferation, survival, migration and changes in cell identity. These signals may involve pathways such as PI3K–AKT, RAS–RAF–MEK–ERK, Wnt–β-catenin, NF-κB and YAP–TAZ. The result is a molecular system capable of translating physical and chemical changes in the tumour environment into instructions that help cancer cells adapt.

The receptor is also unusually complex because the CD44 gene can produce multiple protein forms through alternative splicing. The standard form, often called CD44s, is found in many normal tissues, while variant forms, known as CD44v, contain additional extracellular regions generated by the inclusion of variable exons. These variants can alter how the receptor interacts with growth factors, matrix components and signalling proteins. In several cancers, particular CD44 variants have been associated with aggressive disease, although their abundance and biological significance can differ between tumour types and even between regions of the same tumour.

One of the most closely studied functions of CD44 is its connection to cancer stem-like cells. These cells are not necessarily permanent or identical to stem cells in healthy tissue, but they can display enhanced abilities to self-renew, initiate new tumours and survive stress. CD44-positive populations have been reported in cancers including breast, colorectal, gastric, pancreatic, head and neck and liver malignancies. The review highlights that CD44 is not a universal or definitive cancer-stem-cell marker; instead, its importance depends on the tissue, the CD44 isoform, the surrounding microenvironment and the other markers present on the cell.

CD44 may also help cancer cells undergo epithelial–mesenchymal transition, or EMT, a developmental programme that can give stationary epithelial cells more mobile and invasive properties. During EMT-like changes, tumour cells may lose strong cell-to-cell adhesion and acquire the ability to move through tissue, enter blood vessels and establish distant colonies. CD44 signalling can interact with transcriptional regulators such as Snail, Slug, Twist and ZEB proteins, which are known to control EMT-associated gene expression. This interaction creates a potential molecular bridge between altered cell identity and metastatic behaviour.

The receptor’s effects extend beyond tumour cells themselves. CD44 is present on immune cells, fibroblasts and other stromal populations that occupy the tumour microenvironment. By influencing interactions among these cells, CD44 can contribute to a local environment that supports tumour growth. Its signalling has been linked to inflammatory responses, extracellular-matrix remodelling and the recruitment or functional alteration of immune populations. In some settings, these processes may reduce effective anti-tumour immunity, allowing malignant cells to persist despite the presence of immune surveillance.

Another concern is the relationship between CD44 and resistance to treatment. Cancer cells that express certain CD44 forms may be better equipped to withstand chemotherapy, radiation or targeted drugs through enhanced DNA-repair capacity, altered drug transport, antioxidant protection and survival signalling. CD44-positive cells can also occupy protected niches within tumours, where limited oxygen, nutrient changes and matrix interactions promote a more resilient state. These observations have made CD44 an attractive candidate for therapeutic intervention, but they also underline why simply eliminating CD44-bearing cells may not be sufficient.

Several strategies are being investigated to target the CD44 system. Antibodies and antibody–drug conjugates aim to recognise CD44 or selected CD44 variants and deliver toxic payloads directly to tumour cells. Hyaluronan-based nanoparticles and drug-delivery systems seek to exploit the receptor’s natural binding properties, potentially concentrating treatment in CD44-rich tumours. Other approaches attempt to block the interaction between CD44 and hyaluronan, inhibit downstream signalling, degrade hyaluronan in the tumour environment or target CD44-positive cancer stem-like populations. Each strategy faces technical barriers, including variable CD44 expression, the presence of the receptor in normal tissues and the difficulty of distinguishing malignant from healthy CD44-positive cells.

The review by Oh, Kim, Kim and colleagues presents CD44 as a promising but highly context-dependent therapeutic target. Its expression alone may not reliably predict prognosis or treatment response, because CD44 is shaped by alternative splicing, post-translational modification, cellular location and signals from the surrounding microenvironment. Future treatments may therefore need to combine CD44 targeting with immunotherapy, chemotherapy, radiation or inhibitors of specific signalling pathways. The broader message is that cancer biology cannot be reduced to a single marker: CD44 is better understood as a flexible molecular hub whose effects change with tumour type and disease stage. Mapping those differences could help researchers design more selective therapies while limiting damage to healthy tissues.

Subject of Research: CD44’s roles in cancer progression, metastasis, tumour microenvironment interactions, treatment resistance and targeted therapeutic strategies

Article Title: Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies

Article References: Oh, HJ., Kim, ST., Kim, HJ. et al. “Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.” Experimental & Molecular Medicine (2026). https://doi.org/10.1038/s12276-026-01797-x

Image Credits: AI Generated

DOI: 10.1038/s12276-026-01797-x

Keywords: CD44, cancer progression, hyaluronan, cancer stem cells, metastasis, epithelial–mesenchymal transition, tumour microenvironment, drug resistance, targeted therapy, immunotherapy

At the core of this project is the creation of cancer spheroids, which serve as three-dimensional models that closely mimic the in vivo behavior of tumors. Unlike traditional two-dimensional cell cultures, spheroids offer a more realistic environment that can enhance the understanding of cancer biology and the effectiveness of therapeutic interventions. This method is particularly relevant for teaching students about the pivotal roles that cellular interactions and the extracellular matrix play in tumor development and progression.

The DIY incubator is designed to be cost-effective and easily accessible, making advanced research methodologies attainable for educational institutions with limited resources. This initiative is particularly crucial for fostering scientific curiosity among students, encouraging them to engage directly with the challenges and technologies associated with cancer research. By equipping students with the tools to create and study spheroids, the program inspires a new generation of scientists who are well-versed in modern biomedical techniques.

Moreover, the hands-on experience provided by this project allows students to understand the critical importance of environmental conditions in cell culture. The incubator maintains a stable temperature, humidity, and gas composition, which are vital for the growth of breast cancer spheroids. This control of the culture environment is essential in achieving reproducible and reliable results, a cornerstone of scientific study that students must grasp.

One of the most significant advantages of using a DIY approach is the simplification of the laboratory setup. By stripping down the complexities typically associated with high-tech incubators, students can focus on the fundamental principles of cell culture without being intimidated by advanced equipment. This educational philosophy promotes inclusivity, allowing a wider range of students to partake in meaningful scientific inquiry.

At the same time, this project highlights the ongoing need for innovation in the field of biomedical engineering education. As the landscape of cancer research continues to evolve, educational methodologies must adapt to prepare future scientists for the challenges they will face. The DIY incubator project is a testament to the potential of integrating hands-on learning with contemporary research methodologies, allowing students to experience first-hand the process of scientific discovery.

Critical to the success of this educational endeavor is the incorporation of robust scientific protocols. Students are guided through meticulous steps to ensure the optimal growth and maintenance of breast cancer spheroids. This not only reinforces the importance of precision in research but also enhances their problem-solving skills as they navigate potential challenges that arise during cell culture.

Furthermore, the collaborative nature of this project encourages teamwork among students. By working together to design experiments and troubleshoot issues, participants cultivate essential soft skills that are invaluable in any scientific career. This experience not only enriches their technical knowledge but also prepares them for the collaborative dynamics of real-world scientific research environments.

Importantly, this initiative does not merely serve educational purposes; it also contributes to the broader scientific understanding of breast cancer. By generating and analyzing spheroid cultures, students can investigate the behavior of cancer cells under various therapeutic conditions. This research has immediate implications for developing more effective treatments and personalized medicine approaches.

The hands-on experience gained from this project equips students with a deeper understanding of the complexities of cellular behavior, tumor microenvironments, and treatment responses. They learn to apply theoretical knowledge to practical experiments, reinforcing their understanding of critical concepts in cancer biology, pathology, and pharmacology.

As students delve into this project, they are also exposed to the ethical dimensions of cancer research. Discussions surrounding the implications of their findings and the potential impact on clinical practices foster a sense of responsibility and awareness about the societal consequences of scientific discovery. This ethical component is crucial in shaping responsible future scientists who are cognizant of the broader implications of their work.

In summary, the DIY incubator project for cultivating breast cancer spheroids represents a significant advancement in educational practices within biomedical engineering. By providing students with practical tools and experiences, this initiative not only enhances their educational journey but also contributes to the ongoing battle against breast cancer. As these students graduate and enter the scientific community, they will carry with them the experiences and insights gained from this innovative educational approach, fostering a new era of cancer research that is informed by hands-on experience and ethical consideration.

The relevance of this initiative extends beyond just teaching. It embodies a paradigm shift in how we engage students in the sciences, moving from mere theoretical instruction to immersive experimental investigation. The future of biomedical engineering education appears brighter with initiatives like this one paving the way for more interactive and impactful learning experiences.

Ultimately, fostering an environment that encourages innovation, teamwork, and ethical considerations in science education could transform our collective approach to combating cancer. By empowering students to become active participants in research from an early stage, we not only inspire their scientific curiosity but also equip them with the necessary skills to tackle the complexities of modern medicine.

In conclusion, the DIY incubator project reflects an innovative merging of education and research, offering a practical and ethical framework for students to engage with the urgent challenges posed by breast cancer. As we look to the future, this initiative stands as a model for how educational practices can evolve to keep pace with the demands of contemporary scientific inquiry.

Subject of Research: Cancer Biology and Tissue Engineering

Article Title: Culture of Breast Cancer Spheroids in a Do-it-Yourself Incubator: Introducing Students to Tissue Engineering

Article References: Gallegos-Martínez, S., Pérez-Alvarez, K.A., Trujillo-de Santiago, G. et al. Culture of Breast Cancer Spheroids in a Do-it-Yourself Incubator: Introducing Students to Tissue Engineering. Biomed Eng Education 5, 57–67 (2025). https://doi.org/10.1007/s43683-024-00158-2

Image Credits: AI Generated

DOI: https://doi.org/10.1007/s43683-024-00158-2

Keywords: DIY incubator, breast cancer spheroids, tissue engineering, biomedical education, hands-on learning, cancer research, scientific inquiry.