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# Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)

Cancer drugs with their own mechanisms: tretinoin and arsenic make APL cells mature, asparaginase starves leukaemia cells, bortezomib blocks the proteasome.

Updated Nov 1, 2026

## What they are

A mixed group: the differentiating agents tretinoin and arsenic trioxide for acute promyelocytic leukaemia (APL), the enzymes asparaginase and pegaspargase for acute lymphoblastic leukaemia, and the proteasome inhibitor bortezomib for multiple myeloma.

## Mechanism of action

In APL the PML-RARα fusion protein blocks myeloid maturation; tretinoin (at high levels) and arsenic trioxide both lead to its degradation, so the leukaemic promyelocytes mature. Asparaginase breaks down circulating asparagine, which leukaemic lymphoblasts cannot make well enough. Bortezomib blocks the proteasome, so damaged and regulatory proteins pile up and the myeloma cell dies.

Target: PML-RARα (APL), plasma asparagine, the proteasome

## Key points

- Differentiation syndrome with tretinoin or arsenic trioxide: fever, breathlessness, weight gain, lung infiltrates and effusions; treated at once with high-dose corticosteroids.
- Arsenic trioxide: QT prolongation and torsade de pointes; ECG and potassium and magnesium before and during treatment.
- Asparaginase: allergy (up to anaphylaxis), pancreatitis, thrombosis or bleeding, high glucose and liver injury; pegaspargase lasts longer and is less immunogenic.
- Bortezomib: peripheral neuropathy, low platelets and hypotension; never given intrathecally.

## Drugs in this class

- [**Tretinoin** All-trans retinoic acid taken by mouth for acute promyelocytic leukaemia: it makes the leukaemic cells mature. Watch… Retinoic acid receptor α (RARα), part of the PML-RARα fusion in APL](https://durgical.com/en/pharmacology/tretinoin/)
- [**Arsenic trioxide** An intravenous arsenic compound that cures most acute promyelocytic leukaemia with tretinoin. Key risks: QT… PML-RARα fusion protein (and other thiol-containing proteins)](https://durgical.com/en/pharmacology/arsenic-trioxide/)
- [**Asparaginase** A bacterial enzyme that destroys blood asparagine, which leukaemic lymphoblasts need; a pillar of ALL treatment. Watch… Plasma L-asparagine (the drug is the enzyme L-asparaginase)](https://durgical.com/en/pharmacology/asparaginase/)
- [**Bortezomib** The first proteasome inhibitor, a cornerstone of multiple myeloma and also used in mantle cell lymphoma. Its main… 26S proteasome, chymotrypsin-like site (β5 subunit)](https://durgical.com/en/pharmacology/bortezomib/)
- [**Pegaspargase** Asparaginase bound to polyethylene glycol: it lasts longer and causes fewer allergies than the native enzyme; used in… Plasma L-asparagine (the drug is a pegylated L-asparaginase)](https://durgical.com/en/pharmacology/pegaspargase/)
- [**Carfilzomib** Second-generation intravenous proteasome inhibitor (an epoxyketone) for relapsed multiple myeloma. Watch the heart… 26S proteasome, chymotrypsin-like site (β5 subunit of the 20S core)](https://durgical.com/en/pharmacology/carfilzomib/)
- [**Ixazomib** Oral proteasome inhibitor, a capsule taken once a week with lenalidomide and dexamethasone for relapsed multiple… 26S proteasome, β5 subunit (PSMB5) of the 20S core](https://durgical.com/en/pharmacology/ixazomib/)

## Others in the class

- carfilzomib
- ixazomib
- calaspargase pegol

## Test yourself

Think of the answer, then tap the question to see it.

## Which translocation defines the leukaemia treated with tretinoin and arsenic trioxide?

t(15;17), which creates the PML-RARα fusion in acute promyelocytic leukaemia.

## Why are leukaemic lymphoblasts sensitive to asparaginase?

They lack enough asparagine synthetase and depend on asparagine from the plasma, which the enzyme destroys.

## Which toxicity most often limits bortezomib?

Peripheral neuropathy.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - TRETINOIN capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c4ae9d9-c2a0-4995-a27a-e3f0f0284db9) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - ARSENIC TRIOXIDE injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c99b01b4-67ff-4793-8375-fe3a21c6c9be) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - BORTEZOMIB injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=decb5d94-2ea2-48d8-b08b-3196b24c0ed3) (DailyMed (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/classes/other-antineoplastics/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/other-antineoplastics/