Dr Naidoo L4 Flashcards
What is personalized medicine in the context of cancer treatment, and how has it changed the approach to cancer therapies?
Personalized medicine refers to a medical approach that tailors treatments to individual patients based on their specific genetic, molecular, and clinical characteristics. In the context of cancer treatment, personalized medicine involves using molecular tests to predict clinical outcomes and selecting treatments that are targeted to the unique characteristics of a patient’s tumor. This approach has changed cancer therapies by moving away from broad-based cytotoxic drugs and towards more specific and targeted therapies that aim to interfere with molecules involved in tumor growth and progression.
Provide examples of targeted therapies used for specific cancers, and explain how they work.
Glioblastomas: Temozolomide is used in combination with radiation therapy and chemotherapy. Methylation status of the MGMT gene promoter is tested, and patients with methylated MGMT promoters benefit from temozolomide.
Breast Cancer: HER2-targeted therapies like Herceptin are used for breast cancers with HER2/neu gene amplification. Immunohistochemistry and FISH staining are used to determine HER2 status.
MiRNAs: MicroRNAs (miRNAs) are small noncoding RNAs that play a role in gene regulation. They can act as oncomirs (oncogenic miRNAs), TSmiRs (tumor suppressive miRNAs), or MetastamiRs (miRNAs associated with cancer metastasis).
Explain the concept of promoter methylation and how it is utilized in the context of glioblastoma testing.
Promoter methylation is a molecular process where methyl groups are added to the DNA sequence in the promoter region of a gene. In the context of glioblastoma testing, the methylation status of the MGMT gene promoter is assessed. MGMT is a gene involved in repairing DNA damage caused by chemotherapy. Methylation of the MGMT promoter leads to gene silencing, which is beneficial for patients with glioblastoma. This is because the silencing of MGMT enhances the effectiveness of the chemotherapy drug temozolomide, making the tumor cells more vulnerable to treatment.
Describe the process of miRNA replacement therapy and its significance in cancer treatment.
MiRNA replacement therapy involves introducing specific miRNAs into cancer cells that have decreased expression of those miRNAs. This approach aims to restore the normal functions of these miRNAs, which can have tumor-suppressive effects. In certain cancers, the loss of inhibitory miRNA activity contributes to the activation of oncogenes. MiRNA replacement therapy adds back the missing miRNAs to counteract this effect and potentially reverse the cancer cell’s phenotype. This therapy holds promise as it can help restore gene regulatory networks and signaling pathways that have been disrupted in cancer.
How are HER2/neu gene amplification and its protein expression determined in breast cancer, and why is it important for treatment decisions?
HER2/neu gene amplification and protein expression in breast cancer are determined using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) staining. IHC assesses the intensity and extent of HER2 protein staining, while FISH examines gene amplification. HER2 overexpression indicates a pivotal role in cell growth and can lead to malignant transformation. Approximately 30% of breast cancers have HER2 amplification. Treatment decisions are based on the level of HER2 expression, with strongly positive cases (3+) being treated with targeted therapies like Herceptin.
How do miRNAs contribute to cancer as diagnostic and prognostic biomarkers? Provide an example.
MiRNAs play a significant role as diagnostic and prognostic biomarkers in cancer. Aberrant miRNA expression is a common feature of cancer cells, and specific miRNAs are being considered as potential biomarkers for diagnosis and prognosis. For instance, certain miRNAs are associated with neoplastic transformation, tumor progression, invasion, and metastasis. Monitoring the expression levels of these miRNAs in patient samples can provide valuable information about the stage and aggressiveness of the cancer, aiding in treatment decisions and predicting patient outcomes.
