USP2 Regulation — An Alternative for Cancer Therapy
Key Terms
- P-53 — A tumor suppressor gene that inhibits tumors from growing
2. USP2 (Ubiquitin Specific Peptidase 2)/VPRBR pathway — A pathway that regulates when the P-53 gene is turned on or off
3. PD-L1 (Programmed Ligand Death 1)— Gene that regulates the number of T-cells made.
4. PD1/PD-L1 Blockade — Antibody that inhibits the number of T-cells that are made.
The Problem
Cancer is undoubtedly one of the most destructive diseases in this world. It is the second leading cause of death in the world, and it is also an incurable disease as of today. On a molecular level, cancer is caused by mutations in the DNA of cells, which disrupts normal cell processes such as cell division, growth, and cell death. Cancer has the ability to spread uncontrollably and invade other places within the body, making it more challenging for cancer patients and doctors to fight against it. Chemotherapy and drug therapy are frequently used to fight cancer. Although these options can get rid of cancer, there is always the potential of accidentally hurting healthy cells in the body. Today, scientists are constantly studying how cancer starts at a molecular level in order to find ways to prevent and (hopefully) cure the spread of cancer.
Experiment
In order to understand how cancer begins, looking at what genes in the DNA are mutated is always a good first step. In almost 65% of cancer cells, the P-53 gene is mutated and causes cancer cells to grow uncontrollably, ultimately creating tumors.
Researchers and scientists from the Columbia University Health Sciences Center aimed to suppress the growth of tumor cells in mice in order to create a possible therapeutic option for human patients. These scientists used USP2 inhibitors mixed with a PD1/PDL1 blockade to completely stop tumors from forming in mice. How exactly does this work?
To begin with, the USP2-VPRBR pathway regulates the expression of the P-53 gene. Most cancer cells are developed whenever there is an overexpression of this pathway, stopping the normal function of the P-53 gene, whose purpose is to suppress tumor growth. More specifically, the USP2 gene is important for the stabilization of the VPRBR pathway. By using USP2 inhibitors, USP2 is inhibited, causing the destabilization of VPRBR and ultimately leading to more expression of P-53. However, these researchers knew that USP2 inactivation causes more expression of PDL1, a side effect of inhibiting USP2.
PDL1 is a gene that is important for stopping T-cells from attacking healthy cells in the body. T-cells aren’t the problem however. T-cells are also important for targeting cancer cells. Whenever there is a high expression of PDL1, it stops the creation of T-cells, allowing cancer to thrive without the help of these cells. To combat the increased expression of PDL1, scientists used a PD1/PD-L1 blockade, which inhibits the expression of PDL1.
Ultimately, the scientists increased the expression of P-53 via USP2 inhibition and increased the number of T-cells made by using the PD-1/PD-L1 blockade to inhibit the high expression of PDL1.
Results and Discussion
With these two combinations, the scientists were able to completely regress the formation of tumors in mice, meaning that all tumor-bearing mice were able to survive long-term. Additionally, the mice were observed with minimal to no toxicity against normal cells and tissues. Toxicity is an important factor in developing the most optimal solution that doesn’t cause life-damaging side effects. With that being said, this combination could be a possible therapeutic option. However, more investigation and tests are needed to be done to understand whether or not these combinations are effective for the treatment of human cancer patients in clinical trials. As the search for a cure for cancer continues, one can only hope that these findings will be important for the creation of a cure that will cure all cancers.
