Advancing cancer research by improving patient sample quality

September 07, 2021     

Bristol Myers Squibb places a strong emphasis on human genetics and large-scale datasets to understand the basis of human disease and the biological impact of medicines. Patient samples play an integral role in the development of new medicines as a source of clinical, real-world and translational data to advance the research pipeline and guide therapeutic development. While critical to advancing research, the practical aspects of sample collection can be challenging. Bristol Myers Squibb is committed to improving this process by working together with industry, academia and medical institutions to share knowledge and process learnings to increase the quality of patient sample data in cancer research. Bristol Myers Squibb is also dedicated to respecting the privacy of patients, following all applicable rules and laws related to patient information and confidentiality.

The critical role of patient samples in cancer research

Patient samples are any type of biopsy or specimen (e.g., tissue, blood, etc.) collected from a patient by their healthcare team. Samples are routinely collected during patient care and treatment and can then be studied by their treatment team and other researchers. Patient samples can provide a wealth of information for cancer research, guiding aspects from early target identification to biomarker analysis for patient stratification. The data patient samples provide are unique and cannot be duplicated by other methods of research. 

The tumor microenvironment (TME), which is the complex network of cells and tissues that surround a tumor, is integral to cancer cell survival and growth. This environment is specific to the cancer residing inside the human body. As such, studying cancer cells in vitro – cell lines that can be studied outside of the body in a laboratory setting – or in other models may, in some instances, fall short when results are extrapolated to human tumors. 

“The translation between what's going on in a test tube or Petri dish to what's going on in a human patient is really not a direct comparison,” said Scott Ely, scientific director, Translational Pathology. “There are many examples of a drug having been developed that is effective in vitro or in other models but that doesn't work in humans.”

In many instances, an effective way to understand what is happening in a particular patient’s cancer, at a specific point in time, is to take a sample from the patient’s body — blood, tissue, etc. — anywhere the cancer cells may exist. This biopsy provides the opportunity to interrogate the properties of the tumor as well as the interactions of various cell types and the landscape within which the tumor exists. Specific anti-cancer targets can be identified and examined, helping researchers to study and understand the role a target plays in the TME and how it may contribute to cancer cell growth. 

Scientists can take these samples and study them for biological markers — biomarkers of the particular type of cancer. Data from these biomarkers can also be used to pinpoint specific patient populations in whom a therapeutic could be effective, or ineffective, to better match patients to specific therapies.

“We use biopsy samples to understand whether a specific protein is expressed in the tumor cells or other cells in the microenvironment,” said Scott Ely, scientific director, Translational Pathology, Translational Medicine. “Understanding the expression of certain targets tells us whether a patient is a good candidate to respond to a certain therapy or not and can help get them into the right trial. Moreover, understanding the expression of a target, not only in the tumor, but in immune cells and normal cells, will give us a better understanding of expected off-target effects.  It also helps us understand the mechanism of action of a drug.  With good biopsies, we actually know what is going on inside a patient.” 

To stay ahead in the cancer fight, it is also critical to profile patient samples over time throughout treatment to discover mechanisms of cancer resistance that can be further mitigated. For this purpose, Ely emphasizes the utility of blood-based liquid biopsy collection.

These learnings apply at all stages of preclinical and clinical development and are key to the application of translational medicine, which integrates scientific understanding into decision-making with the goal of accelerating the discovery and development of new medicines for patients.

The unique challenges of working with patient samples

Patient samples can provide a wealth of information for drug development, but working with these delicate specimens can present challenges. The most pressing challenges to the industry involve controlling pre-analytic variables and obtaining a workable sample size.

tissue sample in microscope

Pre-analytic variables include everything that happens to the sample prior to researchers running their analysis, or lab tests. This can include the time the sample spends outside of the patient prior to being stabilized, as well as the temperature at which it is stored. For example, if a sample is taken on a Friday, but not processed until Monday, the composition of that sample can change significantly during that time. These kinds of pre-analytic variables may alter what researchers see when they run assays, which may result in misguided conclusions about what is happening in the tumor and the TME. This is especially true with evermore sensitive and high-depth experimental methods, such as single-cell transcriptome profiling, that are being adopted for patient sample research. In order to get the most accurate picture of what is happening inside the patient at the time the sample is taken, these variables must be understood and, preferably, tightly controlled.  

It’s very important that the amount of sample provided by the patient is sufficient to run the laboratory tests. Inadequate sample size can limit the ability of researchers to perform tests on the sample as originally intended, making the efforts on the part of the patient (providing the sample), the healthcare provider (taking the sample) and the institution (preserving the sample) irrelevant.

Patient samples are a critical component to scientific and clinical research. Insufficient amount of sample or samples of low quality due to improper storage and handling hinder progress in cancer research. The good news is these challenges can be solved with the development of minimum standards, and increased communication of those standards and coordination between patients, healthcare providers, and the research institutions. 

Working together to improve sample quality and advance cancer research

In recognition of the importance of patient biospecimens to the discovery of new medicines, Bristol Myers Squibb established the industry’s first dedicated, enterprise-wide specimen management organization within its Global Development Operations division in 2020. This group manages biospecimens end-to-end from all clinical trials, globally, from the design of clinical protocol through collection, shipment, testing, storage, and, if patient consent allows, re-use for additional research. This team’s specimen management system also manages ‘digital specimens’ from patients, such as imaging scans like MRIs and PET scans as well as newer applications, like digitized versions of tissue slides. Finally, in recognition of the importance of informed consent, this new organization manages patient consent choices related to the use and re-use of his or her specimens for both discovery and clinical research.

Bristol Myers Squibb is also proud to partner with industry, healthcare professionals and site personnel to help solve challenges with patient samples by facilitating improved communication across the healthcare ecosystem. The company is part of the Precision Medicine Coalition with other industry partners looking to solve challenges in research and medicine, including in patient samples and laboratory specimen management. Scientists at Bristol Myers Squibb are also working across the organization on efforts aimed to better collaborate with institutions that collect samples. These efforts include creating guidelines and materials to help inform collection sites as well as a program facilitating feedback to institutions to troubleshoot and help improve processes. By raising awareness of sample needs for research and developing goals for collection sites for various aspects of the process, industry partners can play an active and collaborative role in increasing the number of high-quality patient samples available for analysis.

“We are very interested in working together to improve the usefulness of samples for patients and research.  We want to be a resource for the whole team at the sites obtaining the samples,” says Ely. “Everyone is working toward a common goal: advancing cancer therapy. The process of obtaining and maintaining high quality samples takes work and coordination, but with effective two-way communication and small tweaks to standard site processes, we have found we can do a great job.”

Bristol Myers Squibb has also looked to partner in broader ways to expand the potential impact and reach of research efforts, including those involving data from patient samples. As one example, Bristol Myers Squibb formed the International Immuno-Oncology Network (II-ON), one of the first global peer-to-peer, academic and industry collaborations that aims to advance cancer research and translational medicine to improve patient outcomes. The company also continues to cultivate a broad, vibrant network of external partners. This includes a collaboration with Boston Medical Center to identify and analyze potential sensitivity and resistance markers in patients treated with standard-of-care checkpoint inhibitors, with the ultimate goal of identifying prognostic and potentially predictive I-O biomarkers in a variety of cancers. 

Selecting the right therapy for a cancer patient may not only depend on cancer type, but also on a host of other factors including the characteristics of the tumor and the interactions taking place in the TME. The ability to collect data and study cancer as it exists in the human system is irreplaceable to researchers, allowing the identification of new pathways, targets and patient populations, all of which contribute to the development of innovative therapies and move forward a singular goal of transforming patients’ lives through science.

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