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New drug overcomes resistance in aggressive breast cancers

icr.ac.uk

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Re: New drug overcomes resistance in aggressive breast cancers

#2
This isn’t ‘evolution busting’, have to laugh at university PR. The drug has modest single agent activity, and is additive with a chemotherapy drug in an animal model (not synergistic). The mechanism of action is a bit interesting, it seems to make cells rush through the cell cycle.

The drug development is going to be complicated. The drug doesn’t work well by itself, so getting the right combination dosing and schedule is crucial. It also only works in some tumours and there is a candidate biomarker, so a clinically meaningful assay has to be developed. There is also no idea about toxicity yet. Long road ahead.

Re: New drug overcomes resistance in aggressive breast cancers

#4
post #2

This isn’t ‘evolution busting’, have to laugh at university PR. The drug has modest single agent activity, and is additive with a chemotherapy drug in an animal model (not synergistic). The mechanism of action is a bit interesting, it seems to make cells rush through the cell cycle. The drug development is going to be complicated. The drug doesn’t work well by itself, so getting the right combination dosing and sched…

what a downer

Re: New drug overcomes resistance in aggressive breast cancers

#5
post #2

This isn’t ‘evolution busting’, have to laugh at university PR. The drug has modest single agent activity, and is additive with a chemotherapy drug in an animal model (not synergistic). The mechanism of action is a bit interesting, it seems to make cells rush through the cell cycle. The drug development is going to be complicated. The drug doesn’t work well by itself, so getting the right combination dosing and sched…

I agree. It looks promising but IIUC it is just a new chemotherapy drug. The general idea of killing cells that reproduce is common in many (most?) of the chemotherapy drugs, so they produce nasty side effects like perhaps killing the bone marrow that also have (healthy) cells with a fast preproduction cicle.

I really don't understand the evolutionary/Darwinian spin. It doesn't make sense, it looks like a buzzword. They just (try to) kill all the cells that reproduce like other chemotherapy drugs.

Re: New drug overcomes resistance in aggressive breast cancers

#6
post #2

This isn’t ‘evolution busting’, have to laugh at university PR. The drug has modest single agent activity, and is additive with a chemotherapy drug in an animal model (not synergistic). The mechanism of action is a bit interesting, it seems to make cells rush through the cell cycle. The drug development is going to be complicated. The drug doesn’t work well by itself, so getting the right combination dosing and sched…

I agree. It looks promising but IIUC it is just a new chemotherapy drug. The general idea of killing cells that reproduce is common in many (most?) of the chemotherapy drugs, so they produce nasty side effects like perhaps killing the bone marrow that also have (healthy) cells with a fast preproduction cicle. I really don't understand the evolutionary/Darwinian spin. It doesn't make sense, it looks like a buzzword. T…

There are even DNA and cell division targeted agents. Colchicine kills cells by messing with DNA segregation between dividing cells. This one appears to promote division? Though I haven’t read all the details.

Re: New drug overcomes resistance in aggressive breast cancers

#9
post #7

Massage those breasts people! Most cancers hardly manifest themselves in parts of the body where there is good blood flow to remove cell waste. Very little cancer that originates in bicep/triceps or quadricep/glutes.

By all means, massage your breasts, but I'm not so sure your hypothesis holds up. The paucity of cancers of skeletal muscle is more likely due to cell type (terminally differentiated without much turnover) rather than vascular supply. Carcinomas of the lung and colon are some of the most prevalent (probably still would be even taking environmental factors into account) and those organs get plenty of blood supply. Leukemias also aren't rare and are literally bathed in blood flow.

Re: New drug overcomes resistance in aggressive breast cancers

#10
post #6

Earlier quoted context omitted.

I agree. It looks promising but IIUC it is just a new chemotherapy drug. The general idea of killing cells that reproduce is common in many (most?) of the chemotherapy drugs, so they produce nasty side effects like perhaps killing the bone marrow that also have (healthy) cells with a fast preproduction cicle. I really don't understand the evolutionary/Darwinian spin. It doesn't make sense, it looks like a buzzword. T…

There are even DNA and cell division targeted agents. Colchicine kills cells by messing with DNA segregation between dividing cells. This one appears to promote division? Though I haven’t read all the details.

I think it doesn't promote cell division directly. IIUC this make the cell during the division to not wait until the chromosomes are correctly split, so the new cell have a high chance of getting a wrong number of chromosome and die. Since the cell doesn't wait until everything is in order, the division is faster.

Form the abstract: https://mct.aacrjournals.org/content/18/10/1696

> In in vivo pharmacodynamic experiments, BOS172722 potently inhibits the spindle assembly checkpoint induced by paclitaxel in human tumor xenograft models of TNBC, [....]

I think the key part is "spindle assembly checkpoint" https://en.wikipedia.org/wiki/Spindle_checkpoint

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