Molecular Fundamentals - Overview of Cancer Treatments and Therapies

surgical therapies can be used for what purposes?

• diagnostic

• staging

staging is important for what?

deciding what treatment is best and for predicting the patient’s prognosis

curative surgery involves what?

the complete removal of the tumor as well as some of the surrounding normal tissue (margins)

what describes debulking?

as much of the tumor is removed as possible, but the entire tumor is not removed; other treatments can then be used to eliminate the remaining cancer cells

what describes palliative surgery?

used to relieve side effects caused by a tumor; can improve the quality of life for patients with advanced cancer or widespread disease

because cancer cells have a high rate of division, chemotherapeutic drugs are what?

designed to target various aspects of the cell cycle

since chemotherapeutics do not specifically recognized neoplastic cells, what can happen?

both normal and abnormal cells can be affected

tissues with a high turnover rate will be severely affected by these drugs, what are some examples?

• GI tract 

• hair follicles

• germ cells

what is vinca alkaloids?

mitotic inhibitor that is a microtubule destabilizer and inhibits their growth

how are taxans mitotic inhibitors? 

they are microtubule stabilizers that bind to the cap on the plus end of the microtubule and prevent GTP to GDP conversion, inhibiting the shrinkage of microtubule

methotrexate inhibits what?

the enzyme that converts dihydrofolate to tetrahydrofolate, which is essential for the the synthesis of thymidine

flourouracil (5-FU) prevents the synthesis of what?

thymidine

anti-metabolites such as methotrexate and fluorouracil (5-FU) are commonly used for what?

to treat leukemias, breast, ovarian, and GI cancers

methotrexate and fluorouracil (5-FU) result in what?

“thymineless death” of cells due to absence of dTTPS and the inability to replicate DNA

DNA damaging agents are primarily mediated by what?

topoisomerase inhibition or DNA intercalation

what are some DNA damaging agents?

• Doxorubicin

• Dactinomycin (actinomycin D)

what does doxorubicin do?

induces free radical species

what does dactinomycin (acitnomycin D) do?

intercalates into the minor groove of DNA double helix and inhibits transcription and can inhibit DNA replication at high doses

what describes targeted therapy?

drugs that block the growth and spread of cancer by interfering with specific molecules that are involved with the growth, progression, and spread of cancer

most targeted therapies are cytostatic, which means what?

they block tumor cell proliferation (rather than induce death of tumor cells)

within targeted therapy, what does small molecule inhibitors refer to?

small compounds that bind to and prevent the activity of their target

within targeted therapy, what does therapeutic monoclonal antibodies refer to?

antibodies that have been modified to effectively bind and inhibit the activity of cancer promoting molecules

small molecule EGFT inhibitors (Afatinib, Eroltinib, Gefitinib) can be used to do what?

treat non-small cell lung cancer

small molecule Raf inhibitors (dabrafenib, vemurafenib) can be used to treat what?

unresectable or metastatic melanoma

small molecule MEK inhibitors (trametinib) can be used to treat what?

unresectable or metastatic melanoma

small molecule inhibitors of CDK4/6 (palbociclib) can be used to treat what?

metastatic breast cancer

Antibody inhibitors of HER2 (trastuzumab) does what?

blocks the dimerization of the HER2 receptor; can be used to treat HER2 positive breast cancer

antibody inhibitors of EGFR (cetuximab, panitumumab) can be used to treat what?

squamous cell carcinoma of the head and neck and metastatic colorectal cancer

antibody inhibitors of VEGF (bevacizumab) can be used to treat what?

metastatic forms of colorectal, cervical, renal cell, and non-small cell lung cancers, as well as glioblastoma

antibodies that induce cell death (rituximab) can be used to treat what?

some types of B-cell non-Hodgkin lymphoma

systemic radiation therapy can be delivered how?

via IV or taken by mouth

systemic radiation therapy can be used to treat what?

thyroid cancer

what are the radioactive isotopes used for systemic radiation therapy?

• iodine

• strontium

• phosphorus

what is a type of internal radiation therapy?

brachytherapy

what is brachytherapy?

radioactive seeds are placed in or near the tumor, giving a high radiation dose to the tumor while reducing the radiation exposure in the surround healthy tissues

brachytherapy can be used to treat what?

some lung cancers and prostate cancer

what describes machine radiation therapy (also known as external radiation therapy)?

high energy rays are directed into the tumor

what are commonly used methods of external radiation therapy?

• gamma knife

• proton therapy

what describes gamma knife?

• several gamma rays are focused on the tumor at the same time, creating a very intense dose of radiation that produces DNA damage that kills the cancer cells; usually one treatment

• typically used for individuals with small to medium brain tumors

cyber knife works similarly to gamma knife besides what?

it uses lower doses of gamma rays and is multiple treatments

what describes proton therapy?

particle beam therapy that utilizes a beam of protons and results in DNA damage in cancer cells

with proton therapy, protons can be ________ focused on the tumor.

precisely

proton therapy is used to treat cancers in which what?

the surrounding tissue needs to be preserved

• prostate cancer

• pediatric brain tumors such as medulloblastoma

what describes cancer immunotherapy?

type of cancer treatment that uses the body’s own immunological defense to eliminate the cancer

cancer immunotherapy involves a class of drugs that have been developed called what?

“checkpoint inhibitors”

with cancer immunotherapy, the checkpoint inhibitors do what?

target molecules that normally work to suppress immune responses and limit autoimmunity

CTLA-4 and B7 normally do what?

suppress immune system

PD-L1 does what?

inhibits PD-1 and is expressed on the surface of tumor cells, preventing the T cell from killing the tumor

what describes lpilipmumab?

a monoclonal antibody that inhibits CTLA-4 and B7, and the inhibition allows the activation of T cells and their recognition of cancer cells

what describes nivolumab?

a monoclonal antibody inhibitor of PD-1, which inhibits the inhibitory interactions between PD-L1 molecules on cancer cells and PD-1 on T cells and allows the T cell to kill cancer cells

inhibition of CTLA-4 and B allows for what?

the activation of T cells and their recognition of cancer cells

inhibition of PD-1 causes what

the inhibition of the inhibitory interactions between PD-L1 molecules on cancer cells and PD-1 on T cells and allows the T cell to kill cancer cells

what describes the process of chimeric antigen receptor (CAR) T-cells therapy?

• remove blood from patient to get T cells

• Make CAR T cells in lab

• grow millions of CAR T cells

• infuse CAR T cells into patient

• CAR T cells bind to cancer cells and kill them