Chromosomal instability is a feature of many advanced human tumors and it’s associated with therapeutic resistance, immune evasion, metastasis, and cancer progression in general. We’ve always thought of chromosomal instability as a marker of tumor progression, but as we got to understand more and more about the consequences of chromosomal instability on cancer cells, it’s become clear that it’s an active driver of cancer progression, of therapeutic resistance, and immune evasion...
Chromosomal instability is a feature of many advanced human tumors and it’s associated with therapeutic resistance, immune evasion, metastasis, and cancer progression in general. We’ve always thought of chromosomal instability as a marker of tumor progression, but as we got to understand more and more about the consequences of chromosomal instability on cancer cells, it’s become clear that it’s an active driver of cancer progression, of therapeutic resistance, and immune evasion. The reason over the past, perhaps, decade that we started to think that chromosomal instability can act as a vulnerability in cancer is that chromosome segregation errors, which underlie chromosomal instability, are actually poorly tolerated in normal cells. And that probably is the main reason why our normal cells have two copies of every chromosome, one copy from the mother and one copy from the father, whereas in cancer cells, you know, this process goes haywire. So what that led to is the insight that cancer cells must have adaptive mechanisms to tolerate chromosome segregation errors, and not just tolerate them, but co-opt them for progression and dissemination and resistance. But by understanding these mechanisms, we’re now able to target what we think is cancer’s Achilles’ heel to prevent these cells from tolerating instability, to enable these cells to consider instability, just like the normal cells do, as a vulnerability, as a liability, and then to elicit a lot of, you know, the protective mechanisms that normal cells invoke when a chromosome missegregation happens. And this can happen at many levels. It can happen at the metabolic level, it can happen at the inflammatory immune level, and it can happen at the cell-intrinsic level and cell division. So overall, chromosomal instability represents a really important and yet untapped opportunity to target many important cancer vulnerabilities.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
