Tumour targeting strategies Flashcards
To be able to describe the 4 major types of cancer
treatments.
Surgery: Surgery involves removing the cancerous tumor or tissue from the body. It is often the first treatment option for many types of cancer, especially those that have not spread to other parts of the body. Surgery may be used alone or in combination with other treatments, such as radiation therapy or chemotherapy.
Radiation therapy: Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. It is often used after surgery to kill any remaining cancer cells, or it may be used as the primary treatment for some types of cancer. Radiation therapy may also be used to relieve symptoms caused by cancer, such as pain or bleeding.
Chemotherapy: Chemotherapy uses drugs to kill cancer cells throughout the body. It may be given by mouth or injected into a vein or muscle. Chemotherapy is often used when cancer has spread to other parts of the body, or when surgery is not possible. It can be used alone or in combination with other treatments.
Immunotherapy: Immunotherapy is a type of treatment that uses the body’s own immune system to fight cancer. It works by stimulating the immune system to recognize and attack cancer cells. Immunotherapy is often used to treat certain types of cancer, such as melanoma, lung cancer, and kidney cancer.
To be able to describe and cite examples of the
different types of chemotherapeutic drugs.
Alkylating agents: These drugs work by damaging the DNA of cancer cells, preventing them from dividing and multiplying. Examples include cyclophosphamide, chlorambucil, and melphalan.
Antimetabolites: These drugs mimic the structure of natural substances that cells need to grow and divide, and they interfere with the cancer cells’ ability to use those substances. Examples include methotrexate, 5-fluorouracil (5-FU), and gemcitabine.
Anthracyclines: These drugs work by interfering with the DNA of cancer cells and preventing them from dividing and multiplying. Examples include doxorubicin, epirubicin, and daunorubicin.
Topoisomerase inhibitors: These drugs work by interfering with an enzyme called topoisomerase, which cancer cells need to divide and multiply. Examples include etoposide, irinotecan, and topotecan.
Mitotic inhibitors: These drugs work by interfering with the ability of cancer cells to divide and multiply. They are often used to treat fast-growing tumors. Examples include paclitaxel, docetaxel, and vinblastine.
Platinum-containing compounds: These drugs work by damaging the DNA of cancer cells, preventing them from dividing and multiplying. Examples include cisplatin, carboplatin, and oxaliplatin.
Cisplatin mechanism of action
Cellular uptake: Cisplatin enters the cancer cells through active transport mechanisms.
Activation: Once inside the cancer cell, cisplatin is activated by the presence of water molecules, which cause it to release reactive platinum ions.
DNA binding: The reactive platinum ions in cisplatin bind to the DNA in cancer cells, forming covalent bonds. This binding causes changes in the DNA structure, preventing the cancer cells from dividing and multiplying.
Apoptosis: The changes in DNA structure caused by cisplatin can trigger a process called apoptosis, which is programmed cell death. This process causes the cancer cells to die and be eliminated from the body.
To understand and be able to describe the various
mechanism of action of vinca alkaloids,
antimetabolites, and targeted therapies.
Vinca alkaloids: Vinca alkaloids, such as vincristine and vinblastine, work by inhibiting the formation of microtubules in cancer cells. Microtubules are important structures in cell division, and their inhibition can prevent cancer cells from dividing and growing. Vinca alkaloids also interfere with the transport of important molecules within cancer cells, leading to their death.
Antimetabolites: Antimetabolites, such as methotrexate and 5-fluorouracil (5-FU), work by mimicking the structure of natural substances that cells need to grow and divide. These drugs interfere with the cancer cells’ ability to use these substances, leading to their death. For example, methotrexate is a folic acid analogue that inhibits the action of an enzyme required for the synthesis of DNA, leading to cell death.
Targeted therapies: Targeted therapies are a group of drugs that are designed to specifically target and inhibit molecules that are essential for cancer cell growth and survival. Examples include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. TKIs, such as imatinib, work by blocking the activity of specific enzymes that are overactive in cancer cells, while monoclonal antibodies, such as trastuzumab, target specific proteins on the surface of cancer cells, inhibiting their growth and division.
To be able to explain the molecular basis of targeted
therapies, and the concept of oncogene addiction.
argeted therapies are a class of cancer treatments that are designed to selectively target cancer cells while sparing healthy cells. The molecular basis of targeted therapies lies in the identification of specific molecules or pathways that are critical for cancer cell growth and survival. By targeting these molecules or pathways, targeted therapies can inhibit cancer cell growth and induce cancer cell death.
The concept of oncogene addiction is based on the idea that cancer cells rely on specific genetic mutations or molecular pathways for their growth and survival. In some cases, cancer cells become “addicted” to these mutations or pathways, meaning that their growth and survival depend on them. This addiction makes these mutations or pathways ideal targets for cancer therapies.
For example, many types of cancer are driven by mutations in genes known as oncogenes, which promote cell growth and division. Targeted therapies, such as tyrosine kinase inhibitors (TKIs), work by inhibiting the activity of specific enzymes that are overactive in cancer cells due to these oncogene mutations. By inhibiting these enzymes, targeted therapies can slow down or stop cancer cell growth and induce cancer cell death.
Another example of targeted therapy is the use of monoclonal antibodies, which can target specific proteins on the surface of cancer cells. For instance, the monoclonal antibody trastuzumab targets the HER2 protein, which is overexpressed in some breast cancers. By binding to HER2, trastuzumab can inhibit the growth and survival of cancer cells that depend on this protein.
To be able to name current cancer treatments that
target specific hallmarks of cancer.
Targeting cell proliferation: Chemotherapy drugs like paclitaxel and cisplatin target rapidly dividing cells, which are characteristic of cancer cells.
Targeting angiogenesis: Angiogenesis inhibitors like bevacizumab and sorafenib block the formation of new blood vessels that tumors need to grow and metastasize.
Targeting apoptosis: Apoptosis-inducing agents like bortezomib and venetoclax induce cancer cells to undergo programmed cell death.
Targeting DNA damage: PARP inhibitors like olaparib and rucaparib target DNA repair pathways in cancer cells, leading to their death.
Targeting immune evasion: Immune checkpoint inhibitors like pembrolizumab and nivolumab block the activity of proteins that cancer cells use to evade the immune system.
Targeting metabolism: Metabolic inhibitors like enasidenib and ivosidenib target metabolic pathways that are altered in cancer cells.
To be able to describe the difference between
synthetic dosage lethality, synthetic lethality, and
lineage dependence, and cite examples of drugs that
harness the cancer liabilities afforded by each of
these concepts.
Synthetic dosage lethality (SDL) is a genetic interaction where the combined effect of two mutations, neither of which is lethal on its own, leads to cell death. Specifically, SDL occurs when a mutation in one gene sensitizes the cell to perturbations in another gene’s expression level. For example, in cancer cells with mutations in the BRCA1 or BRCA2 genes, which are involved in DNA repair, inhibiting the expression of another DNA repair gene, PARP1, can lead to cell death. This concept has been successfully harnessed in the development of PARP inhibitors such as olaparib, which are used in the treatment of certain types of breast and ovarian cancer.
Synthetic lethality (SL) is a genetic interaction where the simultaneous loss of function of two genes leads to cell death, whereas loss of function in either gene alone does not. For example, in cancer cells with a mutation in the KRAS oncogene, which is frequently mutated in several cancers, inhibiting the expression of another gene, such as CDK4 or TBK1, can lead to cell death. This concept has been successfully harnessed in the development of drugs such as palbociclib, which is used in the treatment of certain types of breast cancer.
Lineage dependence is a concept in which a specific gene or genetic alteration is required for the survival or proliferation of cancer cells within a particular tissue type. For example, in melanoma, the oncogene BRAF is frequently mutated, and the use of BRAF inhibitors such as vemurafenib has shown significant clinical benefits in treating this type of cancer. However, these inhibitors have limited efficacy in other cancer types, such as colon cancer, which typically do not harbor BRAF mutations.
What is synthetic lethality
Synthetic lethality occurs when the combination of mutations in two or more genes leads to cell death, while mutations in either gene alone do not have this effect. In other words, the combined effect of the mutations is lethal to the cell, while each mutation alone is not enough to cause cell death.
This concept is particularly relevant in cancer research, where scientists are exploring the use of synthetic lethality to develop targeted therapies. For example, if a cancer cell has a mutation in gene A, and a drug is developed that targets gene B, which is synthetic lethal with gene A, then the cancer cell should be selectively killed while normal cells are spared. This approach has the potential to be more effective and have fewer side effects than traditional chemotherapy.
What is lineage dependance
Lineage dependence refers to the idea that the behavior or properties of a cell or tissue type are dependent on the lineage or developmental history of that cell or tissue. In cancer research, lineage dependence can affect the behavior of cancer cells and their response to treatment. One example of a drug that harnesses lineage dependence is the drug imatinib for the treatment of chronic myeloid leukemia (CML). Imatinib targets a specific fusion protein that is only present in cells of the myeloid lineage, which includes CML cells, but not in normal cells. This selective targeting of the cancer cells based on their lineage dependence allows for effective treatment while sparing normal cells.
To be able to name examples of hormone receptor
targeted therapies including receptor antagonists,
hormone synthesis inhibitors, and degraders.
Receptor antagonists: These drugs block the binding of hormones to their respective receptors, inhibiting downstream signaling pathways. Examples of receptor antagonists include:
Tamoxifen: A selective estrogen receptor modulator (SERM) that is used to treat estrogen receptor-positive breast cancer by blocking the binding of estrogen to the receptor.
Fulvestrant: A selective estrogen receptor degrader (SERD) that binds to the estrogen receptor and induces its degradation, resulting in decreased signaling.
Enzalutamide: An androgen receptor antagonist that is used to treat advanced prostate cancer by blocking the binding of androgens to the receptor.
Hormone synthesis inhibitors: These drugs inhibit the production of hormones that activate their respective receptors. Examples of hormone synthesis inhibitors include:
Aminoglutethimide: An aromatase inhibitor that inhibits the synthesis of estrogen by blocking the activity of the enzyme aromatase.
Abiraterone: An inhibitor of cytochrome P450 17A1 (CYP17A1), an enzyme involved in androgen synthesis. This drug is used to treat advanced prostate cancer by inhibiting the production of androgens.
Ketoconazole: An antifungal agent that also inhibits the synthesis of cortisol by blocking the activity of the enzyme 11-beta-hydroxylase. This drug is sometimes used to treat hormone-dependent cancers, such as breast or prostate cancer.
Degraders: These drugs induce the degradation of hormone receptors, reducing their activity. Examples of receptor degraders include:
PROTACs: A class of drugs that use a bifunctional molecule to recruit an E3 ubiquitin ligase to a specific target protein, resulting in its degradation. For example, ARV-471 is a PROTAC that targets the estrogen receptor for degradation.
Selective estrogen receptor degraders (SERDs): These drugs bind to the estrogen receptor and induce its degradation, resulting in decreased signaling. Fulvestrant is an example of a SERD.
