Hypoxic tumor cell sub-populations are highly resistant to radiotherapy and their presence
frequently causes disease recurrence and death. Here, we described the physicochemical properties required
to develop superior tumor-targeted hypoxia-activated modular prodrugs that liberate extremely
short-lived bis(sulfonyl)hydrazines (BSHs) as reactive cytotoxins, thereby precisely focusing cytotoxic
stress on these radio-resistant hypoxic sub-populations. Therefore, cytotoxic stress will be focused on
radiation resistant areas and thus strongly synergizing with radiotherapy.
Keywords: Hypoxic tumor cell, bis(sulfonyl)hydrazines (BSHs), cytotoxic stress, hypoxic sub-populations, radiotherapy,
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