Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer.

Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits.

Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features.

loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion.

Tuberous sclerosis complex (TSC) is an inherited neurodevelopmental disorder (NDD) with frequent manifestations of epilepsy and autism spectrum disorder (ASD). TSC is caused by inactivating mutations in or tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2) forming a functional complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. This has led to treatment with allosteric mTORC1 inhibitor rapamycin analogs ("rapalogs") for TSC tumors; however, rapalogs are ineffective for treating neurodevelopmental manifestations.

Erratum: Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.

[This corrects the article DOI: 10.1016/j.omtm.