Molecular oncology is aninterdisciplinary medical specialty at the interface ofmedicinal chemistry andoncology that refers to the investigation of the chemistry ofcancer andtumors at themolecular scale. Also the development and application ofmolecularly targeted therapies.
Molecular oncology has identified genes that are involved in the development of cancer. Cancer arises as an abnormality in genomic control, either due to the activation of oncogenes or loss of functioning tumor-suppressor genes. Oncogenes result in an uncontrolled increase in cell proliferation; tumor-suppressor genes act as a brake, leading the cell cycle to stop and promote cell death when necessary.[1] The research combined diverse techniques ranging fromgenomics,computational biology,tumourimaging,in vitro andin vivo functional models to study biological and clinicalphenotypes. Theproteins produced by thesegenes may serve astargets for novelchemotherapy drugs and other cancer treatments, or imaging scans. Scientists use a range of techniques to validate the role of the novel candidate genes in the development of cancer. The ultimate aim is to translate these findings into improved treatment options for cancer patients.[2]
There are many different genes being researched for possible cancer therapies. Among the most studied are thep53 gene and thePTEN gene.[3] These genes are major regulators of thecell cycle and other pathways involved in cellular and genomic integrity. By halting the cell cycle, these genes ensure that genetically damaged cells are not passing on that damage to daughter cells. The cell cycle may be paused and if the damage is severe enough, the p53 and PTEN gene pathways may signal for the death of the damaged cells.[4] Both the p53 and PTEN genes are classified astumor suppressors because their pathways oversee the repair of cells that may replicate out of control with damaged genetic material, eventually leading to cancer growth if not kept in check.[5]Mutations in these genes are seen in more than half of human cancers.[3]
Immunegene therapy is a targeted approach to cancer therapy where actual immune cells of the patient and their genes are manipulated to produce an anti-tumor response.[6] The body's ownimmune system is used to attack the tumor cells, therefore the immune system can naturally attack the specific cancer cells again to in the future if necessary.[7] Many types ofimmunotherapies exist includingbone marrow transplants,antibody therapies, and various manipulations of host immune cells to target and kill cancer cells.Cellular receptors, antigens, andcofactor molecules are some such cellular manipulations to target cancer cells.[6]
Chimeric antigen receptor T cell immunotherapy (CAR-T), possibly combined withcytokines andcheckpoint inhibitors, are a regularly used form of immune gene therapy.[6] CAR-T involves manipulation of a patient's naturalT cells to express a chimeric antigen receptor. This receptor, now on millions of the patient's T cells, recognizes cancerous cells that express specificantigens.[6] Usually, the T cell antigen receptor is inactive but when the receptor recognizes a certain cancerous antigen, the physical structure of the T cell changes to destroy the cancer cell.[8] This is a method of cancer treatment that works on the cellular and molecular level.
Someregulatory proteins, specifically immunecheckpoint inhibitors, have been found to reduce the ability of T cells to multiply within the body.[8] In order to optimize the efficacy of CAR-T gene therapy, these checkpoint inhibitors can be blocked to stimulate a robust anti-tumor immune response, spearheaded by the CAR-T cells.[8] There are various known inhibitory receptors on the CAR-T cell; through manipulation of these receptors and the molecules that bind them, expression of the CAR-T cell can be amplified.[8]
CAR-T cells can also be combined withcytokines to improve the efficacy of the immunotherapy method.[8] Cytokines are messenger molecules that can act on themselves, nearby cells, or distant cells.[8] The signal pathways of these cytokines can be used to enhance CAR-T anti-tumor characteristics.[8] For example,Interleukin 2 (IL2) is a cytokine that acts as agrowth factor for various immune system cells, including T cells. In regards to gene therapy, IL2 can be used to increase replication and dispersing of CAR-T cells throughout the body.[8]
There is room for improvement with this gene therapy approach. Firstly, the antigens of interest expressed on the cancer cells may sometimes be expressed on regular body cells, too.[6] This means the body's T cells will attack its own healthy cells instead of the cancer cells when the antigen is lacking specificity with just the cancer cell.[6] A possible solution to this problem is to include two different antigen receptors on the CAR-T cells to make them even more specific.[6] The second issue with the CAR-T immunotherapy approach is that it can causecytokine release syndrome. This is when an excess ofpro-inflammatory factors are released by the immune system and can cause unpleasant side effects for the patient likenausea and a highfever.[6]
In the past few decades, gene therapy has emerged as a targeted way to treat cancer. Gene therapy introduces foreigngenetic sequences to diseased cells in order to change theexpression of these cancerous cells that are functioning with severely damaged genomes.[6] Cancer cells do not behave like normal cells, so the methods for ridding the body of these cells are more complicated. Manipulation of the pathways controlled by certain genes and their regulators are a large branch of cancer research.
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