1: Ribosome Biogenesis as a Potential Therapeutic Target in KRAS-Mutant Colorectal Cancer / 2: New Insights into Drug Tapering After Achieving Treatment Goals in Rheumatoid Arthritis — A Randomized Controlled Trial of TNF Inhibitor Interval Extension and MTX Reduction (SORAIRO Study)
Science of the Month - April 2026
1: Ribosome Biogenesis as a Potential Therapeutic Target in KRAS-Mutant Colorectal Cancer
Nature Communications.
Tanaka Y, Sakahara M, Yamanaka H, Natsume Y, Kusama D, Kumegawa K, Yoshikawa H, Abe Y, Okabayashi K, Matui S, Kitagawa Y, Koshikawa N, Osumi H, Shinozaki E, Nagayama S, Adachi J, Maruyama R, Yao R.
Molecular targeted therapies targeting KRAS signaling have significantly improved patient prognosis, but they have not yet achieved sufficient therapeutic effects in colorectal cancer. Although clinical studies using multidrug combination therapies have shown improvements in therapeutic efficacy, there are cases where effectiveness is not observed in a certain number of patients. We hypothesized that chemoresistance might be acquired through mechanisms that cannot be observed in two-dimensional cultured cells. Therefore, we investigated the mechanism of chemoresistance acquisition using organoids derived from colorectal cancer patients, which allow for the confirmation of changes in cellular heterogeneity. Our study revealed that a subset of KRAS-mutant colorectal cancer cells transitions to a cellular state with enhanced ribosome biogenesis upon KRAS signaling inhibition, and these cells showed sensitivity to RNA polymerase I inhibition. These results suggest that the enhancement of ribosome biogenesis induced by KRAS inhibition is essential for maintaining this cellular state and could serve as a new therapeutic target. This study clarifies a novel mechanism of drug resistance to KRAS inhibition and is expected to contribute to the development of new therapeutic strategies.
(General and Digestive surgery, Yui Nogawa (née Tanaka))
2: New Insights into Drug Tapering After Achieving Treatment Goals in Rheumatoid Arthritis — A Randomized Controlled Trial of TNF Inhibitor Interval Extension and MTX Reduction (SORAIRO Study)
Annals of the Rheumatic Diseases.
Yuki Imai, Michihito Kono, Tomonori Ishii, Toshihisa Kojima, Shintaro Hirata, Yoshiya Tanaka, Eiichi Tanaka, Koichiro Ohmura, Shunsuke Okamoto, Rumiko Matsumoto, Yuri Sato, Takashi Yamamura, Tsutomu Takeuchi, Yuko Kaneko
In the management of rheumatoid arthritis, drug adjustment after achieving remission or low disease activity is an important theme from the perspectives of infection and adverse event risks, medical costs, and medication burden. This study randomized 149 patients from 58 institutions, whose disease activity was stable under combination therapy with the TNF inhibitor ozoralizumab and the anchor drug methotrexate, into a treatment continuation group, an ozoralizumab dosing interval extension group, and a methotrexate reduction group, and directly compared the progression of disease activity. Regarding the primary endpoint, the maintenance rate of low disease activity at 48 weeks, neither drug reduction group met non-inferiority to the treatment continuation group. However, when limited to cases in remission at baseline, the remission maintenance rate was nearly equivalent across groups, suggesting that drug tapering may be a realistic option for patients who have achieved remission. In most cases of relapse, disease control was regained by returning to the original treatment intensity, and there were no significant differences in physical function or the progression of bone destruction on X-rays. These results indicate that while drug tapering is not suitable for all rheumatoid arthritis patients, it can be considered for patients in remission, providing important implications for drug optimization strategies after achieving treatment goals.
(Rheumatology and Infectious Diseases, Yuki Imai, Yuko Kaneko)