PubMed Health⌕ Search

Biomedical subjects

Natalia Komarova

Publications and source records attributed to Natalia Komarova.

3 recordsLinked to original sources
PubMed2005

Stochastic modeling of drug resistance in cancer.

One of the main causes of failure in the treatment of cancer is the development of drug resistance by the cancer cells. Employing multi-drug therapeutic strategies is a promising way to prevent resistance and improve the chances of treatment success. We formulate and analyse a stochastic model for multi-drug resistance and investigate the dependence of treatment outcomes on the initial tumor load, mutation rates and the turnover rate of cancerous cells. We elucidate the general principles of the emergence and evolution of resistant cells inside the tumor, before and after the start of treatment. We discover that for non-mutagenic drugs, pre-existence contributes more to resistance generation than the treatment phase; this result holds for the case where all drugs are applied simultaneously, and is not applicable for sequential therapy models. The application of mathematical modelling to aspects of adjuvant chemotherapy scheduling. J. Math. Biol. 48(4), 375-422]. Also, we find that treatment success is independent on the turnover rate for one drug, and it depends strongly on it for multi-drug therapies. For low-turnover rates, increasing the number of drugs will increase the probability of successful therapy. For very high-turnover rates, increasing the number of drugs used does not significantly increase the chances of treatment success.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Does cancer solve an optimization problem?

Many cancers are characterized by a high degree of aneuploidy, which is believed to be a result of chromosomal instability (CIN). The precise role of CIN in cancer is still the matter of a heated debate. We present a quantitative framework for examining the selection pressures acting on populations of cells and weigh the "pluses" and "minuses" of CIN from the point of view of a selfish cell. We calculate the optimal rate of chromosome loss assuming that cancer is initiated by inactivation of a tumor suppressor gene followed by a clonal expansion. The resulting rate, p* = 10(-2)per cell division per chromosome, is similar to that obtained experimentally by Lengauer et al. (1997). Our analysis further suggests that CIN does not arise simply because it allows a faster accumulation of carcinogenic mutations. Instead, CIN must arise because of alternative reasons, such as environmental factors, epigenetic events, or as a direct consequence of a tumor suppressor gene inactivation. The increased variability alone is not a sufficient explanation for the presence of CIN in the majority of cancers.

Aneuploidy↗