Cancer cell repopulation after therapy is a phenomenon that leads to therapeutic failure with the consequent relapse of the disease. The process is understudied and mechanisms need to be uncovered. Here we discuss the issue of cancer cell repopulation after chemo- and radio-therapies. We compile evidence alleging that the repopulation of cancer cells can be originated from either cancer stem cells resistant to therapy, cancer cells that in response to therapy become polyploid and thereafter germinate into near-diploid rapid proliferating cells, and/or cells that respond to treatment undergoing senescence as a transient mechanism to survive, followed by the reinitiation of the cell cycle. Approaches targeted to prevent this post-therapy cancer cell repopulation should be uncovered to prevent tumor relapse and thus increase overall survival from this devastating disease.
Hypoxia and faulty vasculature are well-known hallmarks of cancer and in addition to being associated with poor prognosis in patients, these hallmarks are also known to contribute to therapy resistance. In recent years, therapeutics that alleviate hypoxia and promote normalization of vasculature are being explored for cancer therapy. In addition to being hypoxic, cancers such as non-small cell lung cancers exhibit elevated oxidative phosphorylation. Therapeutic strategies that can normalize vasculature and reduce oxidative phosphorylation could greatly benefit the landscape of cancer therapeutics. Here, we highlight a heme-targeting therapeutic strategy that demonstrates significant tumor growth inhibition in non-small cell lung cancer mouse models using multi-spectral optoacoustic tomography.
Early/immature T cell precursor acute lymphoblastic leukemia (EITP ALL) represents a subset of human leukemias distinct from other T-ALL, and associated with poor prognosis. Clinical studies have identified chromosomal translocations involving the NUP98 gene and point mutations of IDH genes as recurrent mutations in patients with EITP-ALL. In a recent study using genetically engineered mice, we demonstrated that cooperation of an Idh2R140Q mutation with a NUP98-HOXD13 (NHD13) fusion gene resulted in EITP-ALL. Highlights of this double transgenic mouse model included the similarity of the immunophenotypic, mutational and gene expression landscape with human EITP-ALL. Additional studies showed that the Idh2R140Q /NHD13 EITP-ALL are sensitive to selective mutant IDH2 inhibitors in vitro, leading to the possibility that these mice can serve as a useful model for the study of EITP ALL development and therapy.
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