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Leiden University Medical Center and Biotech Support Group Report Progress on Stromal Conditioning Biomarkers in Cancer

Leiden University Medical Center and Biotech Support Group Report Progress on Stromal Conditioning Biomarkers in Cancer

Objectives are to characterize and quantify Stroma Liquid Biopsy™ biomarkers so as to correlate to the Tumor-Stroma Ratio scoring methods developed by Leiden University

MONMOUTH JUNCTION, NJ, May 20, 2021 -- Biotech Support Group (BSG) and Leiden University

Medical Center (LUMC), Leiden, The Netherlands, announce progress on their joint goal to correlate

BSG’s patent pending Stroma Liquid Biopsy™ panel of blood-borne biomarkers, to tissue derived

Tumor-Stroma Ratio (TSR) scoring methods developed by LUMC.

Aim and key objectives of the Research Collaboration

Commercial enthusiasm continues for the prospects of measuring cancer non-invasively through

liquid biopsy biomarkers. However, current biomarkers only serve to report tumor burden

mutations, which is not the full picture of progressive disease. The other largely neglected part of

tumors, comes from the cooperation of the normal host response to acquired inflammation at the

primary site, with protease regulation playing a key role. This stromal conditioning assists the

tumor ecosystem, affects resistance to treatment, promotes metastasis and ultimately determines

final outcomes. Thus there is complex interplay between the immune response - both innate and

adaptive, and the malignant cells to shape and modify the surrounding tumor microenvironment

(TME). BSG set out to answer whether such stromal conditioning was measurable in blood sera, to

most if not all cancers, regardless of primary tumor, stage, or metastatic disease. A patent pending

panel of Stroma Liquid Biopsy™ proteomic biomarkers was discovered, which largely reflects how

the innate immune system cooperates in this response.

With these new methods, we aim to characterize and quantify Stroma Liquid Biopsy™ biomarkers in

patient sera, to correlate to Tumor- Stroma Ratio scoring methods developed at Leiden University Medical

Center (LUMC). Despite the introduction of immuno-oncology therapies, the clinical classification

system for predicting metastasis and disease-specific survival is still based on traditional tumor

staging criteria (AJCC/UICC-TNM Classification). This criteria is largely based on tumor cell

autonomous processes, and not the cooperative role of the microenvironment; in the “seed and

soil” concept, cancer cells -called “seed”, survive with the cooperation of the complex

microenvironment of the surrounding stroma, called “soil”.

Nevertheless, it is the crosstalk between the cancer cells and supporting stroma which contributes

to the functional and structural support of the tumor microenvironment, leading to tumor

progression and metastasis.

To better characterize this aspect of tumor biology, LUMC has developed a histopathology based

Tumor-Stroma Ratio (TSR) using stained resected tumor tissue. This is reported to be a strong,

independent prognostic parameter linking tumors with high stromal content to poor prognosis.

TSR continues to be validated in medical research centers around the world for a range of solid

epithelial tumors (

The estimation of TSR is simple and inexpensive, and can be done in routine pathology

investigation of the resected tissue. However, TSR has limitations, as it is mainly conducted

postoperatively, and results from preoperative biopsies remain unclear. Its prognostic value for

tumors other than epithelial is also unclear. Finally, its required invasiveness limits its ability to

monitor the course of disease.

A more comprehensive characterization of stromal conditioning would be very valuable in assessing

tumor aggressiveness. Our hypothesis is that there are two basic tumor types, stroma-low and

stroma-high, that can be classified by a variety of multi-omic signatures. These differences may be

observable at the tissue and blood levels to provide a more refined stratification of the tumor,

prognosis for the patient and potentially new therapeutic strategies that might beneficially

modulate the tumor microenvironment. Blood-based biomarkers, such as those proposed in the

Stroma Liquid Biopsy™ panel, would solve many of current TSR limitations and provide deeper and

less subjective clinical characterization.

To begin supporting this hypothesis, we have begun a multi-omics insilico characterization of

the Stroma Liquid Biopsy™ panel, in colon cancer primary tissues, using publicly available

databases. In soon to be published data, we demonstrate that these two basic tumor types

have strong associations with survival, and are derived largely from the extent of whether the

innate immune response is sufficiently resolved to a functionally competent adaptive T Cell immune

response. Such T Cell competency is often described as ‘Hot’ tumors, and respond better to

immuno-oncology therapies.

“This is a very important collaboration for us as LUMC has been at the forefront in research on the

microenvironment componentry of cancer. While most cancer research is focused on genomic

mutations, even with the introduction of immuno-therapies, we still know very little about each

individual’s hospitality to uncontrolled cellular proliferation. Once we have a much deeper

understanding of this interplay, we can begin to think about modulating inflammation as a

therapeutic option. While complex, that is still not nearly as daunting as genomic mutations that

acquire drug resistance. Furthermore, given the steady nature of stromal cells, such modulation

could result in stable disease and prolonged survival for many if not most cancers. It is quite

rewarding to see how our enrichment products, essential in discovering the Stroma Liquid Biopsy™

panel will now be used further in this collaboration. This is so we can leverage our joint

technologies and capabilities to observe functional reporting features of chronic systemic

imbalances of proteolytic regulation; LUMC will soon be publishing how such imbalances may be

occurring at the tissue level. We believe we will see similar imbalances of protease/inhibitor

function within blood. Unlike other post-translational modifications like phosphorylation, proteolysis

is irreversible. As a result, uncontrolled proteolysis can lead to many disease complications, cancer

just one of many cases. With a proteomic characterization of the inflammatory status in cancer

regardless of primary tumor or clinical stage, we will have gained invaluable insight to

understanding how individuals uniquely adapt to the presence of cancer anywhere in the body, how

individuals can be stratified towards the best treatment options, and how individuals uniquely

respond to medical intervention.” states Swapan Roy, Ph.D., President and Founder of Biotech

Support Group.

Lead authors Drs.Wilma Mesker (Associate Professor) and Cor Ravensbergen (Senior Medical

Student) of the Leiden University Medical Center concur, and state further that, “the tumor-stroma

microenvironment is an important prognostic parameter for patients with epithelial cancer types.

However, tissue staining provides only qualitative information and does not offer any insight into

specific cellular or protein mechanisms that impact survival. We do know that patients with a high

amount of stromal cells in the primary tumor have a bad prognosis and respond worse to current

chemotherapy regimens. Now with the help of BSG’s Stroma Liquid Biopsy™ panel, we have a

working hypothesis that is showing real evidence that unresolved innate immunity plays an

important role in tumor progression. We plan to publish shortly the detailed analysis of this.

Furthermore, with pandemic restrictions subsiding, we will start our LC-MS analysis of the Stroma

Liquid Biopsy™ protein panel in patient sera. Two proteins from the panel are especially noteworthy

as they regulate proteolysis. Through proteomic analysis of their functional sub-forms, we might

determine future therapeutic strategies that can potentially modulate the tumor microenvironment.

Such modulation might improve immuno-oncology treatments, for example turning ‘cold’ tumors to

‘hot’. So we are very excited about the prospects for TSR associations with the Stroma Liquid

Biopsy™ panel reportable from blood serum. This will lead us to more refined segmentation of

cancer patients for personalized treatments.”

To Learn More About Tumour-Stroma Ratio, visit:

To Learn More About Stroma Liquid Biopsy™, download whitepaper at:


To Learn More About BSG’s Albumin & IgG Removal Products, visit:

About Biotech Support Group LLC

Converging with cultural and technological disruptions forthcoming in healthcare, Biotech Support

Group develops methods for cost effective and efficient sample prep essential for these expanding

markets. Following a tiered business strategy, the company continues its growth in the consumable

research products area supporting the rapidly expanding installation of LC-MS instrument and

computational infrastructure. For this market, key products include: AlbuVoid™ and AlbuSorb™ for

albumin depletion, Cleanascite™ for lipid adsorption, and HemogloBind™ and HemoVoid™ for

hemoglobin removal. From these innovations, the company has acquired knowledgebase and

biomarker intellectual property assets that support discoveries of protein markers from blood, with

special emphasis on early detection and personalized medical decisions for cancer patients. For

more information, go to

For business development at BSG,

Contact: Matthew Kuruc 732-274-2866,

About Leiden University Medical Center (LUMC)

As the world changes and its population ages, the number of patients with chronic diseases and

disorders is expanding, while medical costs increase. Therefore, the health of the global population

is one of the biggest challenges of our time. Leiden University Medical Center believes that this

challenge asks for a clear vision and mission. At the LUMC, students are trained in lifelong

innovation and learning. Researchers let themselves be inspired and test their findings directly in

practice. Patients can count on being helped according to the state-of-the-art in science. The LUMC

believes in curing but also in prevention. By collaborating with companies and organizations inside

and outside the region, the LUMC makes innovations and new applications actually possible. Thus

the LUMC serves as an innovator for improving healthcare science and consequently people’s

health. For more information, go to

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Last Updated: 08-Jun-2021