Letter: Kinetic classifications of Antitumour Drugs.

Hill, B T; Price, L A

doi:10.1136/bmj.3.5979.367

Cited by 3 publications

(2 citation statements)

References 2 publications

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“…Comparison of exponential and stationary cell populations following treatment has shown a large difference in their response to most drugs, with a stationary population being often less susceptible, 7 depending on the drug type. Chemotherapeutic drugs have been broadly classified as: (i) ‘cell-cycle-phase specific’, namely, drugs with maximal efficacy at a certain phase of the cell cycle, (ii) ‘cell-cycle-non-phase specific’, namely, drugs that target proliferating cells in all cell-cycle phases, and (iii) ‘non cell-cycle specific’ for drugs that target both proliferating and non-proliferating cells 34 . Most in vitro studies have measured the drug response of continuously exponentially growing cultures, which are typically extremely sensitive to drug treatment despite the cell-cycle variability inherent to exponentially growing cells 60 .…”

Section: Introductionmentioning

confidence: 99%

Persistence to anti-cancer treatments in the stationary to proliferating transition

et al. 2016

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The heterogeneous responses of clonal cancer cells to treatment is understood to be caused by several factors, including stochasticity, cell-cycle dynamics, and different micro-environments. In a tumor, cancer cells may encounter fluctuating conditions and transit from a stationary culture to a proliferating state, for example this may occur following treatment. Here, we undertake a quantitative evaluation of the response of single cancerous lymphoblasts (L1210 cells) to various treatments administered during this transition. Additionally, we developed an experimental system, a “Mammalian Mother Machine,” that tracks the fate of thousands of mammalian cells over several generations under transient exposure to chemotherapeutic drugs. Using our developed system, we were able to follow the same cell under repeated treatments and continuously track many generations. We found that the dynamics of the transition between stationary and proliferative states are highly variable and affect the response to drug treatment. Using cell-cycle markers, we were able to isolate a subpopulation of persister cells with distinctly higher than average survival probability. The higher survival rate encountered with cell-cycle phase specific drugs was associated with a significantly longer time-till-division, and was reduced by a non cell-cycle specific drug. Our results suggest that the variability of transition times from the stationary to the proliferating state may be an obstacle hampering the effectiveness of drugs and should be taken into account when designing treatment regimens.

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Section: Introductionmentioning

confidence: 99%

Persistence to anti-cancer treatments in the stationary to proliferating transition

et al. 2016

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“…More than three decades ago, a distinction was already made between "cycle-specific" and "cell cycle stage-specific" drugs. It was argued that such distinction could provide the means to avoid increased toxicity associated with combination chemotherapy without loss of therapeutic effects [2]. In addition, around that time it was also shown that cell cycle synchronization by pre-treatment with hydroxyurea, a DNA synthesis blocker, could increase the effects of cytostatic drugs like vincristine, predominantly acting in S-phase cells in an in vivo model [9].…”

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confidence: 99%

It takes two to tango, and the right music: Synergistic drug combinations with cell-cycle phase-dependent sensitivities

Lieftink

Beijersbergen

2021

eBioMedicine

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A Randomized Combination Chemotherapy Trial, with and without Adriamycin, in Squamous Cell Carcinoma of the Head and Neck

Shaw¹,

Price²,

Hill³

et al. 1978

Otolaryngol.--head neck surg.

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One hundred seventeen patients with advanced squamous cell carcinoma of the head and neck were treated and placed randomly between two combination protocols, one with adriamycin and the other without. Responses (more than 50% tumor regression) were 67% overall with 63% responding to the combination without adriamycin and 82% responding to the protocol containing it. The increase in the response rate seen with the addition of adriamycin was not statistically significant. The degree of response to chemotherapy was reduced by prior radiotherapy.

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Letter: Kinetic classifications of Antitumour Drugs.

Cited by 3 publications

References 2 publications

Persistence to anti-cancer treatments in the stationary to proliferating transition

Persistence to anti-cancer treatments in the stationary to proliferating transition

It takes two to tango, and the right music: Synergistic drug combinations with cell-cycle phase-dependent sensitivities

A Randomized Combination Chemotherapy Trial, with and without Adriamycin, in Squamous Cell Carcinoma of the Head and Neck

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