Introduction to Human Disease – Chemotherapy Drugs (Modes of Action)

A comprehensive set of flashcards covering chemotherapy drugs and their mechanisms of action as discussed in the lecture notes.

What is the primary aim of chemotherapy drugs in cancer therapy?

To cure specific cancers, reduce tumor size, sensitizing tumors to radiation therapy, and destroy small metastases after surgery.

What is one major limitation of chemotherapy in treating large cancers?

Large cancers are not well perfused by blood, making the tumor's inner part inaccessible to chemotherapeutic agents.

Name a common side effect of chemotherapy.

Hair loss, immune system depression, and nausea.

What type of agents are topoisomerase inhibitors in chemotherapy?

They prevent DNA uncoiling.

What is the role of alkylating agents in chemotherapy?

They interfere with DNA base pairing, leading to strand breaks and halting DNA replication.

What do antimetabolites do in the context of chemotherapy?

They block the formation and use of nucleic acids essential for DNA replication.

What are monoclonal antibodies used for in chemotherapy?

To recognize overexpressed antigens on cancer cell membranes.

How do intercalating agents affect DNA?

They insert into the DNA double helix and distort its structure, inhibiting replication and transcription processes.

What is Doxorubicin primarily used for?

It is one of the most effective anti-cancer agents used to treat a broad spectrum of solid tumors.

What is the mechanism of action of Doxorubicin?

Intercalates into DNA and acts as a topoisomerase II poison, stabilizing the DNA-topoisomerase II complex and triggering apoptosis.

What are the sites where Doxorubicin binds in DNA?

It inserts at GC and CG base pairs, causing a distortion in the DNA structure.

What properties do anthracyclines possess that are beneficial for cancer treatment?

They are naturally occurring antibiotics with anti-cancer properties involving DNA intercalation.

Where is Dactinomycin derived from?

Isolated from S. parvullus.

What is notable about the molecular structure of Dactinomycin?

It contains three fused aromatic rings and two identical pentapeptide side chains.

What is the therapeutic application of Dactinomycin?

Used for the treatment of pediatric solid tumors.

What type of interaction stabilizes Dactinomycin bound to DNA?

Aromatic π-π stacking interactions and hydrogen bonding.

What is the role of tubulin in cell division?

Tubulin is a structural protein that acts as a building block for microtubules during cell division.

What is the effect of Vincristine on cancer cells?

It binds to tubulin, inhibiting the assembly of microtubule structures and stopping mitosis.

What effect does Paclitaxel have on microtubules?

It stabilizes microtubules, blocking normal breakdown and progression of mitosis.

How do alkylating agents form bonds with DNA?

They contain highly electrophilic groups that form covalent bonds with nucleophilic groups in DNA.

What can result from the alkylation of nucleic acid bases?

It can cause miscoding, interstrand, and intrastrand crosslinking.

What nucleophilic groups are most reactive in alkylating DNA processes?

Adenine, guanine, and cytosine.

What is Chlormethine classified as?

A nitrogen mustard alkylating agent.

What type of crosslinking does Chlormethine cause?

It causes both intra- and interstrand crosslinking.

What is the main limitation of alkylating anti-cancer agents?

Toxic side effects due to non-selective alkylation are significant.

What structural feature makes the aziridine ion highly reactive?

The ring strain of the aziridine ring enhances its reactivity with nucleophiles.

What happens during the SN2 reaction with Chlormethine?

A nucleophile attacks the electrophilic carbon in the chloride, facilitating bond formation.

How does chemotherapy achieve its effects on rapidly dividing cancer cells?

By targeting processes essential for cell division and DNA replication.

What is a common therapeutic strategy for treating cancer?

Using a combination of surgery, radiation therapy, and chemical therapies.

Why do some normal cells get affected by chemotherapy agents?

Because some normal cells are also rapidly proliferating and may take up drugs more efficiently.

What key factor influences the choice of chemotherapy drugs?

The specific type, location, and stage of the cancer.

What is the primary mode of action of topoisomerase inhibitors?

To prevent the uncoiling of DNA strands during replication.

Which process is blocked by antimetabolites in chemotherapy?

The formation and utilization of nucleic acids necessary for DNA replication.

How does Doxorubicin lead to apoptosis in cancer cells?

By stabilizing complexes between DNA and topoisomerase II, leading to excessive DNA damage.

What is the broad class of drugs that includes Dactinomycin?

Intercalating agents that can disrupt DNA processes.

How does chemotherapy generally reduce tumor size?

By killing cancer cells or preventing their division.

What is the challenge with using chemotherapy for large tumors?

The inner parts of large tumors may not be accessible due to poor blood perfusion.

What are the common side effects of chemotherapy due to non-selectivity?

Hair loss, suppression of bone marrow function, and gastrointestinal issues.

Name a specific use of Paclitaxel in cancer therapy.

It is approved for treating ovarian, breast, lung, bladder, prostate, melanoma, and esophageal cancer.

What defines the interaction of intercalating agents with DNA?

The ability to insert themselves between base pairs of DNA, disrupting normal function.

What is the expected outcome of DNA alkylation in terms of replication?

It leads to inhibition of replication and transcription.

What is the mechanism employed by drugs like Chlormethine to prevent cell replication?

Through covalent bonding that crosslinks DNA, obstructing its function.

How do alkylating agents affect protein synthesis in non-cancerous cells?

They can lead to toxic side effects by alkylating non-target cells.

Describe the concept of 'crosslinking' as it relates to DNA damage.

Creating covalent bonds that link two strands of DNA together, which can impede replication.

What was the historical significance of Chlormethine in medicine?

It was first used medicinally in 1942 as a chemotherapy agent.

What is one clinical significance of understanding DNA alkylating agents?

Recognizing their potential to cause harmful side effects due to both targeted and non-targeted interactions.