Week Eight – Theory Of The Tumor

This week, I started crunching on my outline and draft for my paper. The good thing was, I got a lot of the background done working on my proposal, so I could largely re-use what I wrote there. The most difficult thing was ignoring the temptation to start searching out more articles to fill in gaps I noticed. Looking for how many dogs are diagnosed with cancer per year in the U.S. (roughly 6 million, by the way), I found a fantastic article on the age of cancer onset based on breed, weight, sex, and cancer type, written by Rafalko et al. (2023).

It led to me a theory of cancer development based on tumor doubling times. In the theory, cancer lays dormant for a period of years, growing in cell number and developing the mutations necessary for metastasis (Rafalko et al. 2023). Even for cancer cells, developing metastatic potential is difficult: human advanced colorectal and pancreatic cancer require ~17 and ~20 years, respectively, to progress from their location of origin (Rafalko et al. 2023). Estimates of latency periods (the time between “the biological initiation of cancer and the medical diagnosis”) are consistent with tumor growth estimates based on reported tumor doubling times: if a cancer takes 30 days to double, and a mass becomes clinically detectable at a volume of ~1 cm3 (containing around 1 billion cells), then one can calculate a latency time of 4 years (Nadler & Zurbenko 2014; Rafalko et al. 2023). Observed clinical timelines of cancer development in humans, and to some extent dogs, have largely validated this tumor-doubling theory (Rafalko et al. 2023).

Given the long development times of cancer implied by this theory, the next objective would be to develop and implement methods of screening for that pre-symptomatic cancer, which could then be confirmed using standard clinical evaluation methods (Rafalko et al. 2023). For this purpose, Rafalko et al. seem to prefer novel liquid biopsy testing (“primarily blood, less commonly urine, cerebrospinal fluid, or other secretions”) (2023; Clifford & Mulin 2022). What a coincidence! CAPMM has done significant work in the development of nanoparticles and their application to detecting blood-based biomarkers.

Other than working on my paper, I passaged my human breast cancer cells; made some more 5% milk solutions, Tris-Glycine buffer, 1X PBS, 70% ethanol, and cell media; and planned out my next week with Purva. She is going to be away next week, so she’s charging me with conducting her experiment! I’ll first passage her two flasks into five, then nine, and on Thursday treat six of those with varying concentrations of a drug. Then I’ll tuck those many flasks away in the incubator to grow over the weekend.

Works Cited 

Clifford CA, Mullin C. Clinical trial to evaluate OncoK9 liquid biopsy test for dogs. 30 Jan 2022 [cited 2 May 2023]. https://www.dvm360.com/view/clinical-trial-to-evaluate-oncok9-liquid-biopsy-test-for-dogs 

Nadler DL, Zurbenko IG. Estimating Cancer Latency Times Using a Weibull Model. Adv Epidemiology. 2014; 2014: 1–8. https://doi.org/10.1155/2014/746769 

Rafalko, Jill M et al. “Age at cancer diagnosis by breed, weight, sex, and cancer type in a cohort of more than 3,000 dogs: Determining the optimal age to initiate cancer screening in canine patients.” PloS one vol. 18,2 e0280795. 1 Feb. 2023, doi:10.1371/journal.pone.0280795