A paradigm shift in CRC treatment
The power of precision. For every cancer patient. Today.
Cancer affects society at a global level, remaining a major cause of death in developed countries. In the past decades, there was significant progress in understanding the biology of cancer and development of molecular targeted therapies. [i], [ii], [iii]. Our knowledge about the functional heterogeneity displayed by tumors has also increased considerably.
But tumor heterogeneity is also what complicates the task of precisely devising the right therapy for the right patient at the right stage [iii]. Until today, we still lack biomarkers indicating improved patient-relevant outcomes, enabling therapy lineup and patient stratification.
According to GLOBOCAN data [iv], [v], colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. In 2020, more than 1.9 million new cases of colorectal cancer and more than 930 000 deaths due to colorectal cancer were estimated to have occurred worldwide. By 2040 the global burden of colorectal cancer will increase to 3.2 million new cases per year (an increase of 63%) and 1.6 million deaths per year (an increase of 73%). Increasing incidence rates are currently observed in younger adults and in countries that are undergoing economic transition. Yet, more than 80% of the new cases projected to occur in 2040 are predicted to occur in our area; and in countries with high or very high levels of the Human Development Index. In colorectal carcinoma it remains of paramount importance to continue researching specifically for the clinical space and focus on actionable results to be implemented in clinical routines [vi]
Biomarker testing before systemic therapy for a stage IV mCRC patient is described by national and international guideline issuing independent medical societies like eg. the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO).
The Problem
There are no biomarkers to evaluate the impact on the tumor by any of the approved main chemotherapy backbones. This affects the vast majority of mCRC patients and cannot be addressed by the current diagnostic tools. Almost all patients will be indiscriminately treated with namely either oxaliplatin-based treatment (FOLFOX), Irinotecan-based treatment (FOLFIRI), regorafenib and Lonsurf (TAS102) treatments.
Lacking better information, a choice of antineoplastic combinations is therefore prescribed also to patients who would eventually benefit more from one of the other combination therapies; others will experience just the side effects as their cancer is not sensitive enough for a main therapy compound.
Impact of the solution
After 14 years of research and development to improve the care for patients with mCRC, the IndiTreat® test is the first CE IVD-marked drug sensitivity test using three-dimensional tumoroids. Tumoroids are derived from fresh samples of colorectal cancer (CRC) tissue that has been obtained from an individual patient’s metastatic colorectal cancer. IndiTreat® determines tumoroid growth inhibition by exposing many hundreds of these mini tumors in vitro to approved antineoplastic drugs and provides the treating oncologist with growth inhibition rates for each of the approved medications that come in question according to standard of care. Generating in vitro hundreds of 3D replicas, called tumoroids, derived from a patient’s tumor, in the Copenhagen central lab, these tumoroids are then exposed to different drugs in order to assess its efficacy, allowing the treating physician to optimize the treatment regime for that specific patient.
Tumoroids enable personalized functional testing. Tumoroids preserve cytology and histology of their original tumors; [i] they preserve protein expression patterns of the original tumor and they exhibit variation in chemosensitivity when exposed to the approved antineoplastic compounds at choice.
Therapies for colorectal cancer stage IV aim at reducing tumor burden. IndiTreat Tests work on a patient’s individual tumor tissue to inform oncologists who want to give absolute priority to therapies with the biggest impact potential, the classic drugs and drug combinations for which there are no guiding biomarkers.
As closely as possible to the real pathophysiology in the individual with a stage IV mCRC, IndiTreat patient-derived 3D tumoroids emulate complex tumor behavior when exposed to antineoplastic therapies.
We are proud to propose IndiTreat® for the clinical routine across Europe to help oncologists and their mCRC patients to know more when it matters most.
[i] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin.
2011; 61(2):69–90. https://doi.org/10.3322/caac.20107 PMID: 21296855
[ii] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013 PMID: 21376230
[iii] Huang M, Shen A, Ding J, Geng M. Molecularly targeted cancer therapy: some lessons from the past decade. Trends Pharmacol Sci. 2014; 35(1):41–50. https://doi.org/10.1016/j.tips.2013.11.004 PMID: 24361003
[iv] Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103. doi: 10.5114/pg.2018.81072. Epub 2019 Jan 6. PMID: 31616522; PMCID: PMC6791134.
[v] Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al.: The global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut, Published online 8 September 2022 – http://dx.doi.org/10.1136/gutjnl-2022-327736
[vi] https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research
[vii] Jeppesen M, Hagel G, Glenthoj A, Vainer B, Ibsen P, Harling H, et al. (2017) Short-term spheroid culture of primary colorectal cancer cells as an in vitro model for personalizing cancer medicine. PLoS ONE 12(9): e0183074. https://doi. org/10.1371/journal.pone.0183074
