Genyous Biomed

Genyous Initiatives to Accelerate Translational Research Through A New Clinical Trials Paradigm

Tumor Tissue Needed for Translational Research

Since the decoding of the human genome understanding of the complexity of human biology has grown significantly. With a more detailed understanding of the biological building blocks called genes and proteins, and their intricate signaling pathways (see Figure 1), we have found that diseases such as cancer are much more complex and heterogeneous than previously thought. With the growing appreciation for the heterogeneous nature of cancer, it is becoming increasingly apparent that, in stark contrast to early practices of one size fits all, future improvements in clinical outcomes will be tied to the ability to identify patient sub-populations that may benefit from more targeted therapeutic regimens. These patient sub-populations will likely be stratified by specific biological traits present in their cancer.

In order to identify these specific traits, scientists require access to representative human tumor tissue. The magnitude of this issue was evident at the Bonnie J. Addario Lung Cancer Foundation’s recent Summit for Survival, a meeting of leading scientists and oncologists from around the world. These scientists met to discuss ways to accelerate the development of solutions for lung cancer. At this meeting, access to human tumor tissue was repeatedly cited as the key bottleneck for the development of new treatments.

Tumor tissue is important not only for discovery but also for pre-clinical testing of new drug candidates. For decades, the prevalent pre-clinical model for testing new cancer agents has been human tumor xenografts in mice. However, these models are not sufficient predictors of efficacy, as evidenced by a 95% failure rate for oncology drug candidates entering clinical trials. One explanation for this extremely high failure rate is that these xenograft tumors are typically derived from human cancer cell lines that have been cultivated on plastic for decades, and thus do not retain the biological diversity that is present in clinical cancer. Consequently, many drugs candidates demonstrated significant activity in non-representative pre-clinical models, only to fail in clinical trials. Readily available transplantable human tumor lines are a key resource needed to make more predictive pre-clinical models prevalent and to increase the success rate of clinical trials.

Biological Specimen Collection During Clinical Trials

In order to identify biological traits that may be indicative of response to new therapies and to have improved predictors of efficacy, human tumor samples, with their biological heterogeneity intact, must be made readily available to investigators. Due to the difficulty of accessing tumor tissue (discomfort to patients and cost of acquisition, storage, and data annotation), it is becoming clear that the best way to address this challenge is to leverage patients who participate in clinical trials.

Genyous proposes a new clinical trial paradigm to collect human biological samples (tumor tissue, serum, urine) to the extent practical in clinical trials, and to make these biological samples (and their associated data) available to investigators seeking to identify biological response markers and to support the proliferation of more predictive pre-clinical models of efficacy.

Funding for Biological Specimen Collection and Management to Facilitate Translational Research

The key challenge is how to fund the costs of acquiring additional biological samples, since these materials will benefit future translational research and not necessarily the sponsor of a given trial. Genyous postulates that this is an ideal opportunity for philanthropy. Funding such initiatives will make meaningful contributions to translational cancer research that has the promise to make an impact in the short term, not decades from now. Deliverables from such efforts can be clearly defined and the results may benefit many investigators for years to come.