Profile
Cancer is a remarkably heterogenous disease at all aspects. This
complexity represents one of the major challenges to develop
precise diagnoses and effective treatments. As such, we work toward
a better understanding of cancer heterogeneity and subsequently
better therapeutic approaches.
1. Cancer Stem Cells.
Over the past decade, cancer cell subpopulations with stem
cell-like characteristics are identified in a wide range of human
cancers, including glioma. These cells are named cancer stem cells
or cancer initiating cells. Cancer stem cells have extended
capacity of self-renewal and can give rise to multiple lineages of
differentiated progenies. Cancer stem cells in glioma and several
other cancer types exhibit preferential resistance toward
conventional chemoradiotherapy and targeted therapies. Therefore,
these cells are blamed to produce recurrent tumors. Our laboratory
has a specific interest in the mechanisms that mediate resistance
to radiation and other therapeutics in glioma stem cells. To this
end, we are currently working on the Notch signaling pathway and
other targets to develop glioma stem cell-targeted strategies.
2. Personalized Medicine.
The oncogene addiction model describes the dependence of certain
cancers on the products of one or a few oncogenes. This model
represents the paradigmatic and most successful rationale for
targeted cancer therapy, which has led to remarkable clinical
success in some molecularly defined subsets of cancers, such as
BCR-ABL-driven chronic myelogenous leukemia, EGFR-mutated non-small
cell lung cancer, and so on. With rapidly evolving new technology,
the Cancer Genome Atlas (TCGA) project and other studies have
greatly improved our understanding of the genetic landscape of
human cancers. Through multi-institutional collaborations, we have
collected a large panel of patient-derived glioblastoma samples. We
are working with other groups to characterize the genome and
epigenome of these samples. On the basis of this platform, we are
now working to identify novel links between tumor genotypes and
phenotypes with a goal to develop molecular-guided treatments.
3. Epigenetic therapy.
Our genetic information is packed in chromatins. Epigenetics
include all chromatin-based events that are essential for
translating genetic information into cellular functions. It has
become increasingly recognized that epigenetic abnormalities are
critically implicated in cancer initiation and progression.
Recurrent mutations altering epigenetic regulation are increasingly
identified in human cancers, including glioblastoma (e.g. IDH1/2,
histone H3). Strikingly, the most recent TCGA study shows that
nearly half of glioblastoma tumors carry at least one mutation that
affects an epigenetic regulator. We recently identified crucial
functions of the BET family bromodomain proteins in proliferation
and survival of glioblastoma with diverse genetic profiles. The BET
proteins are epigenetic readers that specifically bind to
acetylated histones and direct active transcription. Inhibition of
BET proteins by small molecular inhibitors or shRNA shows that BET
proteins are implicated in transcription of many important
oncogenes. As such, targeting BET bromodomain proteins is expected
to generate broad anti-neoplastic effects in glioblastoma and many
other cancer types. On the basis of these findings, we want to
develop more effective combinations that can improve FDA-approved
drugs or drugs currently in pipeline. We are also interrogating the
role of BET bromodomain proteins in other cancer types based on
some key targets genes that we have identified.
Publications
The following timeline graph is generated from all co-authored publications.
Featured publications are shown below:
- LZAP: A break on phosphorylation. Wang J (2017) Cell Cycle 16(19): 1737-1738
› Primary publication · 28118073 (PubMed) · PMC5965456 (PubMed Central) - The MAPK Pathway Regulates Intrinsic Resistance to BET Inhibitors in Colorectal Cancer. Ma Y, Wang L, Neitzel LR, Loganathan SN, Tang N, Qin L, Crispi EE, Guo Y, Knapp S, Beauchamp RD, Lee E, Wang J (2017) Clin Cancer Res 23(8): 2027-2037
› Primary publication · 27678457 (PubMed) · PMC5368030 (PubMed Central) - BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. Loganathan SN, Tang N, Fleming JT, Ma Y, Guo Y, Borinstein SC, Chiang C, Wang J (2016) Oncotarget 7(28): 43504-43517
› Primary publication · 27259270 (PubMed) · PMC5190040 (PubMed Central) - Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma. Hover LD, Owens P, Munden AL, Wang J, Chambless LB, Hopkins CR, Hong CC, Moses HL, Abel TW (2016) Neuro Oncol 18(7): 928-38
› Primary publication · 26683138 (PubMed) · PMC4896540 (PubMed Central) - InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma. Ma Y, Tang N, Thompson RC, Mobley BC, Clark SW, Sarkaria JN, Wang J (2016) Clin Cancer Res 22(7): 1767-76
› Primary publication · 26561558 (PubMed) · PMC4818693 (PubMed Central) - Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. Gong Y, Ma Y, Sinyuk M, Loganathan S, Thompson RC, Sarkaria JN, Chen W, Lathia JD, Mobley BC, Clark SW, Wang J (2016) Neuro Oncol 18(1): 48-57
› Primary publication · 26136493 (PubMed) · PMC4677408 (PubMed Central) - Critical functions of RhoB in support of glioblastoma tumorigenesis. Ma Y, Gong Y, Cheng Z, Loganathan S, Kao C, Sarkaria JN, Abel TW, Wang J (2015) Neuro Oncol 17(4): 516-25
› Primary publication · 25216671 (PubMed) · PMC4483068 (PubMed Central) - Cancer stem cells in glioma: challenges and opportunities. Wang J, Ma Y, Cooper MK (2013) Transl Cancer Res 2(5): 429-441
› Primary publication · 24634854 (PubMed) · PMC3952560 (PubMed Central) - JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer. Song W, Ma Y, Wang J, Brantley-Sieders D, Chen J (2014) Cancer Res 74(9): 2444-54
› Primary publication · 24607842 (PubMed) · PMC4008716 (PubMed Central) - Inhibition of BET bromodomain targets genetically diverse glioblastoma. Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S, Wang J (2013) Clin Cancer Res 19(7): 1748-59
› Primary publication · 23403638 (PubMed) · PMC4172367 (PubMed Central) - LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Wang J, An H, Mayo MW, Baldwin AS, Yarbrough WG (2007) Cancer Cell 12(3): 239-51
› Primary publication · 17785205 (PubMed)