The COC Protocol is an individualized therapeutic approach which seeks to simultaneously target multiple cancer pathways. The COC Protocol may be considered in patients with bladder cancer, adjunctive to conventional cancer treatments.
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This graphic is a summary of some of the potential mechanisms of action reported for agents used in the COC Protocol as reported in the scientific literature. This is an evolving field of research, and this list is not exhaustive.
Targeting Cancer’s Metabolic Pathways
Metabolism is the conversion of food to energy to run cellular processes and construct cellular building blocks. It is widely accepted that the metabolism of cancer cells is usually fundamentally different to that of healthy non-cancerous cells. Altered metabolism is now considered a hallmark of cancer and a new discipline of “metabolic oncology” has emerged (Hanahan and Weinberg, 2000; Hanahan and Weinberg 2011; Bergers and Fendt, 2021).
Cancer cells need large amounts of energy to survive and grow. They commonly use an adaptive process called aerobic glycolysis (the ‘Warburg effect’) to generate the excessive energy they need (Kroemer and Pouyssegur, 2008; Liberti and Locasale, 2016). The COC Protocol aims to target various molecular processes involved in and surrounding aerobic glycolysis and cancer metabolism. It aims to restrict cancer cell energy supply and use, while simultaneously preventing the cells from adapting and using other pathways to take up energy.
As a result of ongoing metabolic stress, the overall metabolic rate of the cancer cell could be lowered (Jang et al., 2013), and cancer cells may become weaker and less able to take in and use nutrients they need from their surroundings (e.g., glucose, lipids, and essential amino acids such as glutamine and arginine). This may potentially make it more difficult overall for cancer cells to survive, grow, spread, and adapt to changing conditions in the body (Martinez-Outschoorn et al., 2017, Jagust et al, 2019, Guerra et al., 2021).
Gradually, metabolically-weakened cancer cells (including more resilient and previously treatment-resistant cells) can potentially become more vulnerable to attack from other cell-killing cancer therapies such as radiotherapy, chemotherapy, and other therapies (Luo and Wicha, 2019, Zhao et al, 2013, Butler et al, 2013).
Using a Combination Approach
Review of peer-reviewed literature suggests that each individual element of the COC Protocol may target cancer cell metabolism in a distinct and potentially complementary way, and we have termed this action ‘mechanistic coherence’. Put simply, mechanistic coherence describes the possibility of attacking a cancer cell from different angles in what may be a synergistic or additive fashion. This type of combination approach in cancer is discussed by Mokhtari et al, 2017, and others.
Selected Bladder Cancer-Related Research Publications
Potential role for metformin in urologic oncology. Sayyid R.K. et al. 2016 PMID: 27195314
Metabolic changes in bladder cancer. Woolbright B.L. et al. 2018 PMID: 29773495
A Clinical Genomics-Guided Prioritizing Strategy Enables Selecting Proper Cancer Cell Lines for Biomedical Research. Shao X. et al. 2020 PMID: 33225250
Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis. Hu J. et al. 2018 PMID: 30045293
Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer. Molenaar R.J. et al 2019 PMID: 31752752
Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells. Kettunen K. et al. 2019 PMID: 31256944
Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation. Greife A. et al 2015. PMID: 25566959
