Targeting oncogenic Myc as a strategy for cancer treatment

The MYC family oncogene is deregulated in>50%of human cancers,and this deregulation is frequently associated with poor prognosis and unfavorable patient survival.Myc has a central role in almost every aspect of the oncogenic process,orchestrating proliferation,apoptosis,differentiation,and metabolism.Although Myc inhibition would be a powerful approach for the treatment of many types of cancers,direct targeting of Myc has been a challenge for decades owing to its“undruggable”protein structure.Hence,alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects,including Myc/Max complex disruption,MYC transcription and/or translation inhibition,and Myc destabilization as well as the synthetic lethality associated with Myc overexpression.In this review,we summarize the latest advances in targeting oncogenic Myc,particularly for cancer therapeutic purposes.

Regulation of cancer cell metabolism:oncogenic MYC in the driver’s seat

Cancer cells must rewire cellular metabolism to satisfy the demands of unbridled growth and proliferation.As such,most human cancers differ from normal counterpart tissues by a plethora of energetic and metabolic reprogramming.Transcription factors of the MYC family are deregulated in up to 70%of all human cancers through a variety of mechanisms.Oncogenic levels of MYC regulates almost every aspect of cellular metabolism,a recently revisited hallmark of cancer development.Meanwhile,unrestrained growth in response to oncogenic MYC expression creates dependency on MYC-driven metabolic pathways,which in principle provides novel targets for development of effective cancer therapeutics.In the current review,we summarize the significant progress made toward understanding how MYC deregulation fuels metabolic rewiring in malignant transformation.

Animal models of T-cell acute lymphoblastic leukemia: mimicking the human disease

T-cell acute lymphoblastic leukemia(T-ALL)is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities.In the past decade,large-scale genomic analysis has shed new light on providing potentially important oncogenic or tumor suppressive candidates involved in the disease progression.Following in silico analysis,functional studies are usually performed to vigorously investigate the biological roles of candidate genes.For this purpose,animal models faithfully recapitulating the human disease are widely applied to decipher the mechanism underlying T-cell transformation.Conversely,an increased understanding of T-ALL biology,including identification of oncogene NOTCH1,TAL1 and MYC as well as tumor suppressor phosphatase and tensin homolog(PTEN),has significantly improved the development of T-ALL animal models.These progresses have opened opportunities for development of new therapeutic strategy to benefit T-ALL patients.In this review,we particularly summarize the mouse and zebrafish models used in T-ALL research and also the most recent advances from these in vivo studies.