Tumor Evolution & Progression

The deadly minority

Unfortunately, in most patients, it is a minority of drug-resistant tumor cells that are present but not detected at diagnosis (or that evolve) that kill patients. No 'omics technology is good enough at single cell analysis to solve this problem.

What is the research problem

Tumors are heterogeneous, & the molecular signatures of the deadly, minority drug-resistant cells are below the noise in all omics approaches. Furthermore, there are multiple mechanisms of resistance to a given therapy.

How will your solution make a difference

Effective cocktails of combination chemotherapies could be devised and used at diagnosis, killing the majority and the minority tumor cell populations when the patient presents, before the tumor burden becomes unmanageable.

What is your proposed solution

Profile tumors (BOTH genomic and proteomics) not only before but also after the emergence of drug resistance (paired samples from the same patient), when the tumor population is dominated by resistant cells whose omic signatures can be detected above noise. Do this on a large scale, not in small R01s. Aggregate data across therapies. Identify combinations of therapies to kill all cells in a tumor before the tumor burden becomes unmanageable.

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Idea No. 102