A Duke University study has shown that metastatic cancer cells can regulate the metabolic function to reproduce in new organs. Cells derived from colorectal cancer have changed their metabolic habits, making full use of fructose in the liver as much as possible. Once the cancer has spread to different parts of the body, the cancer becomes more deadly, but the treatment does not consider the location of its metastasis and is treated according to the original site. From a genetic point of view, colon cancer is colon cancer, no matter where it is transferred. But this does not mean that it cannot respond to the new environment. This response may not be genetic, but metabolic. When cancer cells enter the liver, they are like a child in a candy store, using this abundant new energy to create more cancer cells. In order to feed on fructose, cancer cells need to produce more enzymes that can break down fructose, called ALDOB. Once cancer cells find out how to turn fructose back on, cancer cells will lose control and proliferate. In addition to providing reasons for how cancer proliferates after metastasis, this discovery can also lead to new therapies for metastatic cells. For example, avoiding the use of fructose by eating natural non-processed foods and providing drugs that block the metabolism of fructose may prevent cancer from spreading from other organs to the liver. Since pharmaceutical companies have recently developed new drugs for fructose metabolism to treat metabolic diseases, this crossover therapy may not be far away. Doctors can usually remove the primary tumor. But understanding the causes of cancer metastasis and how to adapt to a new home may provide us with a new weapon against cancer.
Targeting FGFR4 and CD276 with CAR T-cells demonstrates a strong antitumor impact against children rhabdomyosarcoma
Chimeric antigen receptor (CAR) T-cells that specifically target Fibroblast Growth Factor Receptor 4 (FGFR4), a surface tyrosine receptor that is extensively expressed in rhabdomyosarcoma (RMS), are now undergoing clinical research. However, the effectiveness of these CAR T-cells may be hindered by tumor heterogeneity and inadequate activation. In this study, we present a method to enhance the co-stimulatory and targeting characteristics of a FGFR4 CAR through an optimization process. We substituted the hinge and transmembrane domain of CD8 as well as the 4-1BB co-stimulatory domain with the corresponding domains of CD28. The CARs produced exhibit heightened anti-tumor efficacy in multiple RMS xenograft models, with the exception of the RMS559 cell line, which is known for its aggressive nature.
