Hallmarks Q10

Resisting cell death, by upregulating anti-apoptotic proteins such as BCL-2 and downregulating pro-apoptotic proteins like Bax
Rationale: Chemoresistance often involves mechanisms that allow cancer cells to avoid apoptosis, such as the upregulation of anti-apoptotic proteins or the downregulation of pro-apoptotic proteins, reflecting the hallmark of “Resisting cell death.”

A key point here is appreciating that there are lots of “classes” of chemotherapeutic drug that act in different ways (see list below). But the outcome of those different drugs is often induced cell death; the damage caused by the drug is recognised as damage and induces apoptosis. If the drugs stop working, it is likely that the tumour has acquired apoptosis resistance.

• Alkylating agents – cyclophosphamide, cisplatin, ifosfamide – add alkyl groups to DNA leading to DNA cross-linking/strand breaks/disrupting replication and transcription.
• Antimetabolites – methotrexate, 5-fluorouracil, cytarabine – interfere with DNA/RNA synthesis
• Antitumour antibiotics – doxorubicin, bleomycin, mitomycin C – intercalate into DNA or damage DNA and other cellular components.
• Topoisomerase inhibitors – etoposide, irinotecan – inhibits topoisomerase II or I leading to strand breaks and apoptosis
• Mitotic inhibitors – paclitaxel, vincristine – inhibits microtubule function particularly during M phase of cell cycle.
• Hormonal Agents – tamoxifen, anastrozole, leuprolide – block hormone receptors or decrease hormone production.
• Immunotherapy and Targeted agents – Rituximab, Trastuzumab (Herceptin), Pembrolizumab- antibodies targeting specific molecules involved in tumour cell lifecycle.
• Proteosome inhibitors – bortezomib – inhibits the proteosome leading to the accumulation of misfolded proteins

Q10 – final one of this quiz – A new anticancer drug inhibits a receptor tyrosine kinase (RTK) involved in promoting cell motility and invasion. Which hallmark of cancer does this drug target, and what is its expected impact?