How an innovative, data-driven approach is revolutionizing drug discovery for solid tumors

Developing therapies for solid tumors remains a challenging task due to the heterogeneity of tumor tissues and the high variability between individual patients. Collecting tissue samples to analyze the differences between healthy and tumor tissues is a promising method. However, significant results depend on the quantity and quality of the tissue samples combined with analytical, computational, and biochemical expertise to identify new therapeutic targets and potential drug candidates.

Current therapies for solid tumors remain suboptimal, often resulting in poor clinical outcomes and severe side effects. Progress in finding new therapies has been slow, primarily because most drug development projects rely on screening existing ligand collections against known, established therapeutic targets. Identifying novel targets and suitable drugs could lead to true breakthroughs, increasing efficacy and reducing side effects. Cancer tissue biobanks combined with a detailed knowledge of the differences between tumor and healthy tissue and a deep understanding of tumor heterogeneity are cornerstones for developing new treatments.

The role of biobanks in solid tumor drug discovery

Biobanks – collections of tissue samples from cancer patients – have been established worldwide in recent decades and can serve as valuable starting points for discovery. However, biobanks vary considerably in size and quality. Many are still maintained in the same way as they were established when histopathologic analysis by microscopy was the only available method and mass biomolecule analysis technologies were just emerging. 

State-of-the-art analyses of biomolecules such as messenger RNA, long non-coding RNA, micro RNA, or proteomics have significantly higher sample collection and processing requirements. In particular, the time that elapses between sample collection – typically during surgery – and storage in appropriate media or at low temperatures (the so-called “ischemia time”) has been shown to be critical for molecular readout. 

A recent study of colorectal cancer tissue compared samples with 10 and 20 minutes of ischemia time. After 20 minutes, 22% of the mRNA and 53% of the proteins displayed changed expression patterns compared to the 10-minute fraction. Phosphoproteins, which can provide insight into cellular pathways, were shown to be even more fragile, with 86% lost after 20 minutes.

Besides sample quality, sample quantity is crucial to obtaining meaningful data from cancer tissue. A sufficient number of samples are needed to ensure statistically relevant data. In addition, an adequate amount of matched healthy tissue must be collected whenever possible. For example, in colorectal cancer, samples of nearby intestinal mucosa that are not contaminated with tumor cells should be collected to enable comparative studies of healthy and cancer tissue.

In addition, the tumor tissue sample must be large enough to extract as much information as possible from the heterogeneous structure of a tumor. This is essential to understand the individual tumor and identify potential new therapeutic targets.

A breakthrough approach to solid tumor drug discovery

Over the past twenty years, Indivumed Therapeutics, a precision oncology biotech company based in Hamburg, Germany, has established a proprietary approach to identify new targets and pave the way for solid tumor drug discovery breakthroughs.

A comprehensive, high-quality biobank

A comprehensive, high-quality biobank serves as a valuable source of scientific data. To ensure the quality and quantity of the tissue samples, the company has established strict quality standards. Today, Indivumed collaborates with hospitals around the world to ensure that samples are processed by trained personnel directly in the operating room.

The tissue samples are collected and stored using a variety of methods that allow microscopic studies, molecular analyses, and cultivation of individual cells. These high-quality tissue archives are complemented by clinical information for up to 10 years, facilitating the correlation of molecular data with clinical patient outcomes. 

State-of-the-art molecular analyses

State-of-the-art molecular analyses and sequencing are performed on the tissue samples to study a range of essential modalities, including genomics, transcriptomics, proteomics, phosphoproteomics, and microRNA. 

Biomathematical and statistical computing

The scientists at Indivumed perform multivariate analyses of the “omics” data to identify patterns, interaction networks, and the “molecular machinery” controlled by potential new targets. 

Proprietary tools based on biomathematics, biophysics, and artificial intelligence (AI) prioritize the target candidates and determine their druggability based on the scientific insights gained, combined with publicly available structural data or protein folding models. AI-assisted virtual ligand screening is then performed to identify the first hit candidates. All information generated in these analyses is collected and fed into the database.

“We use biophysical information, biomathematical tools, and AI to filter for proteins that are both specific for cancer cells and amenable to drug binding, increasing the chances of finding targets that can be drugged with low toxicity and high efficacy,” explained Landgrebe. 

Biochemical validation in patient-derived cell culture

The high-quality tissue samples archived in Indivumed’s unique biobank allow tissue resection and cultivation of patient-derived cancer cells. Using this individual tumor cell culture, identified targets are validated and characterized in terms of protein type, biochemical characteristics, cellular location, and biological function. 

In addition, the company establishes drug screening assays for cell-free and cell-based compound screening and validates first hits.

“We understand that working with a patient-derived cell culture rather than immortalized cell lines is crucial. This allows us to create models that are closer to the biological reality of the tumor. We can test whether knocking out a gene leads to a phenotype with slowed growth or reduced invasiveness, increasing the chances of finding a real target,” stated Landgrebe.

Achieving results: The therapeutic success of Indivumed’s approach

Indivumed is uniquely positioned with a comprehensive, high-quality biobank collected over more than twenty years according to the strictest standards and supported by detailed clinical follow-up data. Molecular and biochemical data are constantly added to the database.

The company combines the molecular information obtained from patient samples with deep biomathematical, statistical, and biochemical expertise to generate screening-ready packages that comprise a novel, characterized, and validated target with a high probability of successful therapeutic development. A patent is filed for each package, which serves as a starting point for collaborating with pharmaceutical partners for high-throughput screening and chemical hit refinement.

“We believe that our approach is successful because we already have targets in the pipeline that are completely novel, and patent filing is on its way. So we are excited to be able to identify novel targets in solid tumor therapy, contributing to more effective and less toxic cancer treatments,” concluded Landgrebe.

Learn more about how your solid tumor drug screening project can benefit from partnering with Indivumed.

Image Courtesy: Indivumed Therapeutics