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by Dr. C.H. Weaver M.D. updated 5/2022

The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancer’s DNA that are driving a specific cancers growth. Precision cancer medicines and immunotherapies can be used both instead of and in addition to chemotherapy to improve treatment.

CancerConnect Community490 General

Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. By testing an individual’s cancer for specific unique biomarkers doctors continue to develop new precision medicines. All newly diagnosed individuals should discuss NGS-biomarker testing with their physicians. Individuals with endometrial (uterine) cancer not previously tested can also undergo genomic testing to determine whether newer precision cancer medicines are a treatment option

Genetic Mutations

Not all endometrial cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing is performed to test for certain genetic mutations or the proteins they produce because the results can help select treatment including newer precision cancer medicines designed to attack specific breast cancer cells with specific genetic mutations. Several precision cancer medicines and immunotherapy drugs have been recently approved for the treatment of advanced endometrial cancer or are been developed in clinical trials.

HER 2 Positive Uterine Cancer About 30% of all uterine serous carcinomas test positive for HER2/neu, a receptor protein that is also over-expressed in about 10% of all breast cancers.HER2 is a gene that encodes for the receptor tyrosine-protein kinase erbB-2 which is amplified with an increased copy number in several cancers. Amplification of ERBB2 promotes tumorigenesis and pathogenesis of several human cancers. Precision cancer medicines that target HER2 bind to and block HER2 keeping it from driving tumor growth. The HER2 pathway is a biological pathway involved in cellular replication and growth that occurs in some women with endometrial cancer. These “HER2-positive” cancers can be targeted with several precision cancer medicines target and block the HER2-protein.

Checkpoint Inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells. Checkpoint inhibitors are most effective in individuals with a high tumor mutational burden (TMB) A diagnostic test to measure the level of PD-L1 is available.

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DKN-01 is a monoclonal antibody precision cancer medicine that targets the DKK1 protein, which modulates Wnt/beta-catenin signaling. DKK1 is known to play a role in cancer cell signaling and mediating an immunosuppressive cancer microenvironment by boosting the activity of myeloid-derived suppressor cells and down regulating natural killer ligands on cancer cells which help prevent cancer cell growth.

General PMF Newsletter 490

Estrogen Receptors: The uterus is an organ that is highly sensitive to estrogen hormone levels, and thus the growth of endometrial cancer is also sensitive to the presence of hormones. Hormone therapy for endometrial cancer has long included the use of progesterones—such as hydroxyprogesterone, medroxyprogesterone, and megestrol—because the cancer cells have receptors for these agents. Individually, these hormones can produce response rates of 20 to 29%; however, they may be more effective when combined with other anti-estrogen drugs or chemotherapy. Ibrance belongs to a class of drugs known as kinase inhibitors that work by blocking the action of enzymes called kinases. Kinases are involved in many cell functions, including cell signaling, growth, and division. These enzymes may be too active or found at high levels in some types of cancer cells and blocking them may help prevent cancer cells from growing. Specifically, Ibrance inhibits cyclin-dependent kinase (CDK) 4 and 6. These kinases are involved in the growth of Estrogen Receptor (ER)-positive breast, endometrial and other cancers.