I'm editing an e-Book on novel strategies for late-stage solid cancers, especially so-called "differentiation therapy": non-toxic treatments designed to promote differentiation of the tumor in order to slow down its growth. If you'd like to contribute a chapter, please let me know.
Recent report strongly suggests the cytoskelton regulator MKL-1 as the potential therapeutic target to induce the trans-differentiation of undifferentiated osteosarcoma cells into mature adipocytes. Induction of adipocyte differentiation results in disruption of actin stress fibres through downregulation of RhoA-ROCK signalling. The consequent rapid increase in monomeric G-actin leads to the interaction of G-actin with MKL1, which prevents nuclear translocation of MKL1 and allows expression of PPARγ followed by adipogenic differentiation.(Nature Communications 5, Article number: 3368 doi:10.1038/ncomms4368)
Furthermore, Nakayama K et al. have published several papers to suggest the clinical importance to get awaken the dormant cancer stem cells, which otherwise are responsible for latent relapse and distant metastasis. The ablation of Fbxw7 gene results in the prevention of ubiquitin-proteasome degradation of c-Myc, Notch1, and CyclinE, all of which are involved in the promotion of cell cycle. Thus, the inhibition of three Fbw7 isoforms has the possibility to get rid of quiescent CSCs and induce differentiation in the tumor tissues.
Only a suggestion. I think we should go to the edge of chaos, in small situations that may however offer general models.
Recent article , which I enclose, highlights the involvement of retinoic acid in the regression that normally occurs in keratoacanthoma. I also attach an article among many: "Retinoid Differentiation Therapy for Common Types of Acute Myeloid Leukemia".
Keratoacanthoma is a squamous cell carcinoma that arises from hair follicle and probably has kept functioning genes that regulate the proliferation and regression.
PEComas, tumors that I study, prototypes of a hyperactivation of mTOR due to mutation of TSC2, regress with treatment with rapamycin and its analogues. This happens probably turning a large epithelioid cell in a particular smooth muscle cell with ER and PgR and other endocrine activity. Currently therapy with rapamycin and analogs is assessed and used in a large number of tumors.
http://www.nature.com/ncomms/2014/140326/ncomms4543/full/ncomms4543.html
http://www.hindawi.com/journals/lrt/2012/939021/
David, Great Topic for your book. We need to talk. I will call you after the Holidays.....Raouf
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