Transforming Preclinical Oncology: How Reaction Biology is Revolutionizing Cancer Research

One of the greatest challenges in oncology research is developing preclinical cancer models that accurately reflect human disease. The industry has long relied on subcutaneous tumor models for early-stage drug testing. These models, which involve injecting cultured tumor cells under the skin of mice, are convenient and cost-effective and play an essential role in early in vivo characterization. However, these models are limited in their ability to replicate the complexity of human tumors.

To enhance clinical relevance, researchers leverage orthotopic models, in which tumor cells are transplanted into the corresponding organ in mice where they originally grew in humans, preserving key biological interactions. However, these models are more technically demanding, leading researchers to accept higher failure rates from contract research organizations (CROs) that offer orthotopic testing. As a result, this increased failure rate contributes to greater animal use and waste generation.

Recognizing these limitations, Cheryl Davis, General Manager of US In Vivo Services, and her team at Reaction Biology have adopted a more innovative approach, in line with Reaction’s commitment to deep scientific understanding and quality. Their efforts have led to the development of procedurally sophisticated orthotopic bladder and ovarian cancer models that more accurately mimic human tumor environments, resulting in higher success rates. These improved models are already helping pharmaceutical and biotech companies make more informed, confident decisions about which compounds to advance to clinical trials.

In this interview, Cheryl shares insights into how these orthotopic models were developed, the challenges her team overcame, and why these methods are poised to improve cancer research.

The limitations of traditional subcutaneous and orthotopic preclinical cancer models are well-documented. What drove you to develop Reaction Biology’s orthotopic bladder and orthotopic ovarian cancer models?

Cheryl: The biggest challenge in preclinical oncology research is creating physiologically relevant models that accurately mimic human tumors. Subcutaneous models have traditionally been the industry standard because they’re easy to establish and inexpensive, but unfortunately, they don’t capture the complexity of patient tumors. They have a role to play in early discovery, but researchers also need more advanced orthotopic models.

Take bladder cancer, for example. In humans, bladder tumors originate on the surface of the bladder wall, interacting with the surrounding microenvironment. However, subcutaneous models implant tumor cells under the skin, an environment that lacks these crucial interactions.

Moreover, most current orthotopic bladder models involve injecting bladder cancer cells into the bladder muscle wall. While this more straightforward technique is adequate for mimicking muscle-invasive bladder cancer, it’s a poor representation of non-muscle invasive bladder cancer (NMIBC), which accounts for 70-80% of all bladder cancers. So, we felt that we clearly needed to tackle the complicated task of developing a more sophisticated orthotopic model and the associated techniques and methods based on a thoughtful understanding of NMIBC biology. And that stems from our fundamental ethos at Reaction Biology.

Can you share a specific challenge you and your team faced while developing these models and how you overcame it?

Cheryl: One of the biggest hurdles was ensuring that tumors would grow in their natural environment. For our bladder cancer model, we had to develop a technique that allowed tumors to successfully form superficially on the bladder wall rather than deeper within the bladder wall or subcutaneously. We designed an orthotopic bladder cancer model where we instill tumor cells directly into the bladder using a catheter.

To make this process effective, we had to develop several techniques to improve success, including pretreating the bladder with specific agents that gently disrupt the endothelial lining to make the surface more receptive to tumor cell adhesion. This step was critical—it allowed tumors to form where they naturally occur, closely mimicking human bladder cancer. It took a lot of trial and error, but once we got it right, the results spoke for themselves.

Beyond its ability to better replicate human tumor environments, how has this model directly influenced drug development and clinical trial outcomes?

Cheryl: Our model has had a huge impact. It has been validated in multiple studies, and clients have successfully obtained FDA approvals. Several pharmaceutical and biotech companies have used our model to test experimental therapies, and some of those treatments have now progressed into clinical trials.

Unlike many CROs, we don’t rely on a one-size-fits-all approach. We integrate knowledge from multiple sources in the literature, combining these insights to create a highly optimized system. Clients frequently tell us that no one else has successfully replicated these models, reinforcing their importance in advancing cancer research.

How has your model evolved to accommodate new treatment strategies with the shift toward target therapies?

Cheryl: The rise of targeted therapies has dramatically changed how we think about bladder cancer models. Traditionally, our approach relied on immunocompetent mice, which meant we had to use mouse-derived tumor cells to prevent tumor graft rejection. However, as the field has shifted toward therapies targeting the specific biology of human bladder cancer, we needed a way to incorporate human-derived models.

To address this, we developed a xenograft model using immunocompromised mice, which allowed us to implant human bladder cancer cells. This transition wasn’t as simple as just switching out the cell lines. Human tumor cells behave differently, requiring us to rethink our pre-treatment strategies, incubation methods, and tumor growth monitoring techniques.

What were some of the biggest challenges in making this transition?

Cheryl: One of the biggest challenges was ensuring that these tumor cells could successfully adhere to and grow in the mouse bladder environment. With mouse-derived tumors, the immune system plays a critical role in tumor interactions, but with human tumors in an immunocompromised system, we had to compensate for the absence of these components.

We adjusted our pretreatment process to enhance cell adhesion and fine-tuned our incubation methods to optimize tumor take rates. It’s not an apples-to-apples transition—human cell lines require a different approach to achieve consistent tumor growth. We had to rethink how long the cells incubate in the bladder, how they interact with the endothelial lining, and how to optimize their chance of forming viable tumors.

Although this approach removes the mouse immune system from the equation, we incorporate human immune engraftment to better reflect real patient conditions and allow researchers to test drug candidates in a system that more accurately mirrors human cancer progression. Since many new compounds in development specifically target human tumor biology, this adaptation has been crucial in keeping our models translationally relevant.

Today, we’ve successfully generated instillation tumors using human cell lines, and our clients have found this innovation incredibly valuable. Many have told us that no other CRO has been able to replicate our success in this area, reinforcing the impact of our model on bladder cancer research​.

You’ve also spoken about the limitations of orthotopic ovarian cancer models. Can you elaborate on how your team’s approach changes how researchers study tumor progression?

Cheryl: Absolutely. Ovarian cancer research is another area where we have made significant advancements. Historically, ovarian cancer models have suffered from poor translational relevance. Some of the most commonly used cell lines, SKOV3 and OVCAR3, have only been available as subcutaneous models, making it challenging to study how tumors develop in their natural environment.

Rather than trying to force these cell lines into an environment where they struggle, we leveraged their natural biology to create a more representative model. First, we allowed tumor cells to grow and accumulate in the peritoneal cavity, where they form tumor-infiltrated fluid—similar to the ascites seen in advanced ovarian cancer patients.

We then harvested this fluid and, through numerous rounds of selection, isolated the most aggressive tumor cells and reintroduced them into the ovary itself. This created tumors that developed in their natural location, offering a much more relevant orthotopic ovarian cancer model for drug testing.

This “fluid-to-function” approach has been incredibly successful. We presented this work at a major oncology conference, and the feedback from researchers has been overwhelmingly positive.

Beyond the models themselves, is there anything else that sets Reaction Biology apart from other CROs?

Cheryl: I can confidently say it’s our commitment to client service and the quality of our research reports. Other CROs often leave clients to figure out the results on their own. But we take a different approach—we go beyond just providing numbers by delivering comprehensive, thoroughly analyzed reports that help our clients make informed decisions.

When we assemble a report, it’s not just a data dump. We make sure to include detailed explanations of the experimental conditions, tumor growth patterns, statistical analyses, and most importantly, how the findings translate into clinical relevance.

We also maintain open communication throughout the study process. If something unexpected happens—like a tumor responding unpredictably to treatment—we don’t just send over the data and leave the client to figure it out. We work with them directly, helping to interpret the results and discussing the best next steps. At the end of the day, our goal isn’t just to provide results—it’s to help our clients truly understand and apply their data in a meaningful way.

If you could fast-forward five years, what do you hope will be your team’s most significant impact on cancer treatment research?

Cheryl: Looking ahead, we are focused on expanding our metastases model research, particularly in brain and bone models. One of the most impactful projects we’re working on is developing a new brain tumor model that ensures the blood-brain barrier remains intact during tumor implantation.

Traditionally, researchers implant tumor cells directly into the brain. This process can unintentionally disrupt the blood-brain barrier, making it easier for drugs to penetrate the brain than it would be in a real patient. This can create an artificially high success rate in preclinical testing, only for those same treatments to fail in human trials. We want to change that. By developing a model that maintains the natural integrity of the blood-brain barrier, we aim to provide more accurate and reliable drug testing results, increasing the likelihood of clinical success.

We’re collaborating with other groups on an exciting project that uses contrast MRI to study real-time changes to blood-brain barrier permeability. This project could provide major insights into how tumors influence the barrier and how we can better design drugs to target brain tumors effectively. It’s a big step forward, and I can’t wait to see where this research takes us.

Bridging the Gap Between Research and Real-World Impact

Reaction Biology’s bladder and ovarian cancer models are reshaping preclinical oncology research. By prioritizing physiological relevance, experimental rigor, and continuous innovation, Cheryl and her team are helping researchers push promising therapies into clinical trials and ultimately improve patient outcomes. These innovative models represent a major leap forward for pharmaceutical and biotech companies looking to accelerate drug discovery.

Ready to take the next step? Contact one of our experts to learn how these cutting-edge in vivo models can accelerate your drug development program, and let’s discover together.

Cheryl Davis is a leader in preclinical oncology research, serving as General Manager of US In Vivo Services at Reaction Biology. With over a decade of experience in oncology model development, drug discovery, and lab operations, she has been instrumental in advancing in vivo cancer models that improve drug efficacy predictions for clients. She holds a Master’s in Laboratory Animal Science from Drexel University and a Bachelor’s in Animal Bioscience from Penn State University.