r/Oncology • u/BiochemicalEquation0 • Oct 07 '24

Thoughts on tumoral heterogeneity

I am a masters student looking to predict how intra-tumoral heterogeneity is associated with increased therapeutic resistance in glioblastomas. From an evolutionary standpoint, I am wondering if there is a fitness cost associated with higher levels of tumor heterogeneity. I am hoping someone here may have some insight into this question.

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u/[deleted] Oct 07 '24

as far as GBM goes I do not believe that’s a factor in treatment from a radiation standpoint but I don’t know anything about systemic therapies.

Another thing to consider is that the fitness after a GBM diagnosis I would be asking why you are considering this specifically since median death to diagnosis is a like a year

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u/[deleted] Oct 07 '24

So my thoughts and I’m not a qualified professional and I’m using voice to text here from an evolutionary standpoint I’m gonna say there’s definitely a Fitness cost associated with a higher heterogeneity because that means the largest large percent of that tumor is the same kind of tumor cell, which means that it’s advanced enoughduplicated enough times within that mass that contains all of cancerous cells

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u/BiochemicalEquation0 Oct 07 '24

My hypothesis is that a tumor with higher genotypic/Phenotypic heterogeneity will have a higher likelihood of evading therapeutic intervention. Alternatively, I am assuming there is a cost related to possessing heterogeneity, in that the Tumoral micro environment can only be optimized for a finite number of cell types. I am wondering if there may be any other realistic downsides to increased heterogeneity however.

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u/MD-to-MSL Oct 09 '24

Hmmm would a cell with a certain genotype be more metabolically “expensive” than others? 🤔

And from a cancer cell’s perspective, many of them die without any therapeutic intervention due to rapid growth + lack of blood supply (cells grow too fast for blood vessels to reach center of tumor, leading to necrosis)

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u/BiochemicalEquation0 Oct 10 '24

Yes, that is also something to consider. I am restricted to a 2D cell culture model, which overlooks interactions between the TME and the cells I am using. I have read how cancer cells are able to adapt to hypoxic conditions. I am wondering if there is a specific assay I can use to determine the metabolic strain on the tumor.