Viewing Cancer Treatment as a Game to Find Strategies That Improve Patient Outcomes

Game theory-wise treatment plans to advance the standard of care include  men with advanced prostate cancer

August 9. 2018. Game theory can be used to identify potential flaws in current cancer treatment approaches and to select new strategies to improve outcomes in patients with metastatic cancer, according to a review study published online today, August 9, in JAMA Oncology.

Authored by a mathematician, an evolutionary biologist, and clinical physicians from the Moffitt Cancer Center and Maastricht University in the Netherlands, the study challenges decades-old methods. The usual method of treating metastatic cancer involves repeatedly administering the same drug(s) until disease progression. The drugs are given according to Maximum Tolerated Dose (MTD), i.e. the highest dose of a drug or treatment that does not cause intolerable side effects. The maximum tolerated dose is decided via clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

“Current treatments for metastatic cancers, by giving the same drug repeatedly at the maximum tolerated dose, can inadvertently increase the speed with which cancer cells can evolve effective counter measures and then regrow,” said Robert A. Gatenby, M.D., co-director of Moffitt’s Center of Excellence in Evolutionary Therapy, one of the leaders of this new line of research. Continue reading “Viewing Cancer Treatment as a Game to Find Strategies That Improve Patient Outcomes”

Nuclear Gatekeeper Could Block Undruggable Prostate Cancer Targets

Nuclear Pores
The DNA in cell nuclei is stained blue, with the nuclear pores surrounding the nuclei in yellow. Proteins that influence which genes are turned on or off must first pass through these yellow gatekeepers to access the DNA. Blocking these pores could offer a way to target undruggable molecules in cancer. Credit: Labs of Veronica Rodriguez-Bravo, and Josep Domingo-Domenech at Jefferson (Philadelphia University + Thomas Jefferson University)
The DNA in cell nuclei is stained blue, with the nuclear pores surrounding the nuclei in yellow. Proteins that influence which genes are turned on or off must first pass through these yellow gatekeepers to access the DNA. Blocking these pores could offer a way to target undruggable molecules in cancer. Credit: Labs of Veronica Rodriguez-Bravo, and Josep Domingo-Domenech at Jefferson (Philadelphia University + Thomas Jefferson University)

August 9, 2018. Certain molecular drivers of cancer growth are “undruggable” – it’s been nearly impossible to develop chemicals that would block their action and prevent cancer growth. Many of these molecules function by passing cancer-promoting information through a gate in the nucleus, where the instructions are carried out.

Now researchers at the Sidney Kimmel Cancer Center – Jefferson Health have found a way to block the nuclear gates used by these molecules, and have shown that this inhibition can halt aggressive prostate cancer in mice implanted with human tumors.

Co-led by Veronica Rodriguez-Bravo, PhD, and Josep Domingo-Domenech, MD, PhD, this research is published in Cell August 9, 2018.

Verónica Rodríguez and Josep Domingo-Domenech
Verónica Rodríguez and Josep Domingo-Domenech

“We found that a particular gatekeeper, the nuclear pore protein called POM121, traffics molecules that boost tumor aggressiveness,” Dr. Rodriguez-Bravo said. “Blocking this gatekeeper prevents several molecules from reaching their targets in the nucleus, thus decreasing tumor growth.” The researchers also showed that blocking POM121 transport helps restore chemotherapy efficacy in pre-clinical models of the disease.

Continue reading “Nuclear Gatekeeper Could Block Undruggable Prostate Cancer Targets”