Tumour heterogeneity
[3] The heterogeneity of cancer cells introduces significant challenges in designing effective treatment strategies.
In turn, this has the potential to guide the creation of more refined treatment strategies that incorporate knowledge of heterogeneity to yield higher efficacy.
[4] Tumour heterogeneity has been observed in leukemias,[5] breast,[6] prostate,[7][8][9] colon,[10][11][12] brain,[13] esophagus,[14] head and neck,[15] bladder[16] and gynecological carcinomas,[17] liposarcoma,[18] and multiple myeloma.
The models are not mutually exclusive, and it is believed that they both contribute to heterogeneity in varying amounts across different tumour types.
Stem cell variability is often caused by epigenetic changes, but can also result from clonal evolution of the CSC population where advantageous genetic mutations can accumulate in CSCs and their progeny (see below).
[30] Multiple types of heterogeneity have been observed between tumour cells, stemming from both genetic and non-genetic variability.
A more common source is genomic instability, which often arises when key regulatory pathways are disrupted in the cells.
Some examples include impaired DNA repair mechanisms which can lead to increased replication errors, and defects in the mitosis machinery that allow for large-scale gain or loss of entire chromosomes.
Researchers have shown that convergent mutations affecting H3K36 methyltransferase SETD2 and histone H3K4 demethylase KDM5C arose in spatially separated tumour sections.
Similarly, MTOR, a gene encoding a cell regulatory kinase, has shown to be constitutively active, thereby increasing S6 phosphorylation.
The heterogeneous dynamic mechanochemical processes regulate interrelationships within the group of cellular surfaces through adhesion.
[36] The biological phenomena of mechanochemical heterogeneity maybe used for differential gastric cancer diagnostics against patients with inflammation of gastric mucosa[37] and for increasing antimetastatic activity of dendritic cells based on vaccines when mechanically heterogenized microparticles of tumor cells are used for their loading.
[38] There is also a possible methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on nanobubles conglomerates with drugs in the tumour.
This represents the destruction of initial non-resistant subclonal populations within a heterogeneic tumour, leaving only resistant clones.
In multiple myeloma, genetic analyzes of the tumor is used to detect risks markers such as specific mutation, deletion, insertion etc.
A study from 2023 [43] using single cell showed that subclones with risks marker are present in some patients from the diagnosis but in such low frequency that they are not detectable by standard genetic routine assessment.
Due to the genetic differences within and between tumours, biomarkers that may predict treatment response or prognosis may not be widely applicable.
While the problem of identifying, characterizing, and treating tumour heterogeneity is still under active research, some effective strategies have been proposed, including both experimental and computational solutions.
