About 30% of patients experience relapse after treatment, possibly because of our inability to identify and eliminate the cancer stem cells.Zhang et al. recently investigated these cells in the SHH subgroup of medulloblastoma and identified drugs that may target them.
Finally, several metabolic pathways known to be reprogrammed in cancer cells are detected as prognostic pathways including glutamate metabolism in SHH subgroup, pentose phosphate pathway and TCA cycle in Group 3, and folate-mediated one carbon-metabolism in Group 4.
Recent findings have revealed that a small proportion of lung cancer cells expressed an abnormal full-length Shh protein, associated with cancer stem cell features.
WNT, TGF/SMAD, NOTCH, and SHH are fundamentally different signaling cascades, but their choreographed activation is strongly associated with cancer development and progression.
Prognostic biomarkers and models identified were validated in an independent, demographically matched cohort (n=70) of medulloblastoma patients with non-WNT/non-SHH standard-risk disease treated with conventional therapies (maximal surgical resection followed by adjuvant craniospinal irradiation [all patients] and chemotherapy [65 of 70 patients], at UK Children's Cancer and Leukaemia Group and European Society for Paediatric Oncology (SIOPE) associated treatment centres between 1990 and 2014.
Mutational inactivation of Shh receptor Patched (Ptch) and a downstream gene Suppressor of fused (Sufu), both of which are negative regulators of the pathway, increases susceptibility to cerebellum cancer in humans and mice.