New Target for Prostate Cancer Resistant to Anti-Hormone Therapies

“Prostate cancer becomes deadly when anti-hormone treatments stop working. Now a new study suggests a way to block the hormones at their entrance.

“Researchers from the University of Michigan Comprehensive Cancer Center have found that a protein called BET bromodomain protein 4 binds to the hormone androgen receptor downstream of where current therapies work – targeting androgen receptor signaling.

“This could mean that when prostate cancer becomes resistant to current treatments, it might remain sensitive to a drug that targets BET bromodomain proteins. Results appear inNature.”

Editor’s note: The drug described in this story, JQ1, will likely soon be offered to prostate cancer patients through clinical trials.


Dicerna Pharmaceuticals Initiates Phase 1 Study of DCR-MYC in Patients with Solid Tumors and Hematological Malignancies

“Dicerna Pharmaceuticals, Inc. DRNA +0.67% , a leader in the development of RNAi-based therapeutics, today announced the initiation of a Phase 1 dose-escalating clinical study of DCR-MYC, (also known as DCR-M1711), in patients with solid tumors, multiple myeloma, or lymphoma. DCR-MYC, Dicerna’s first drug candidate to enter clinical testing, is a Dicer Substrate siRNA (DsiRNA) that targets the driver oncogene MYC, which is central to the growth of many hematologic and solid tumor malignancies. Dicerna is investigating DCR-MYC in a variety of tumor types with the initial focus on hepatocellular carcinoma.”

Editor’s note: This new drug may hold promise for people with lung cancer or melanoma, as well as other cancer types.


Dicerna Pharmaceuticals Initiates Phase 1 Study of DCR-MYC in Patients with Solid Tumors and Hematological Malignancies

“Dicerna Pharmaceuticals, Inc. DRNA +0.67% , a leader in the development of RNAi-based therapeutics, today announced the initiation of a Phase 1 dose-escalating clinical study of DCR-MYC, (also known as DCR-M1711), in patients with solid tumors, multiple myeloma, or lymphoma. DCR-MYC, Dicerna’s first drug candidate to enter clinical testing, is a Dicer Substrate siRNA (DsiRNA) that targets the driver oncogene MYC, which is central to the growth of many hematologic and solid tumor malignancies. Dicerna is investigating DCR-MYC in a variety of tumor types with the initial focus on hepatocellular carcinoma.”

Editor’s note: This new drug may hold promise for people with lung cancer or melanoma, as well as other cancer types.


Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non-Small Cell Lung Cancer

The recent discovery, in hematologic malignancies, that BET bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven NSCLC with BET inhibition. We performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cells lines harboring KRAS and/or LKB1 mutations.

Bromodomain inhibition comprises a promising therapeutic strategy for KRAS mutant NSCLC with wild-type LKB1, via inhibition of MYC function.


PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy

“Although 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to PI3K-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces Myc phosphorylation and protein accumulation. We show that PDK1-PLK1-Myc signaling is critical for cancer cell growth and survival and small molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting Myc-dependency. Intriguingly, PDK1-PLK1-Myc signaling induces an embryonic stem cell-like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self renewal. Finally, we show that PLK1 inhibitor synergizes with mTOR inhibitor to induce synergistic anti-tumor effect in colorectal cancer by antagonizing a compensatory Myc induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting Myc-associated tumorigenesis and therapeutic resistance.”


PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy

“Although 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to PI3K-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces Myc phosphorylation and protein accumulation. We show that PDK1-PLK1-Myc signaling is critical for cancer cell growth and survival and small molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting Myc-dependency. Intriguingly, PDK1-PLK1-Myc signaling induces an embryonic stem cell-like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self renewal. Finally, we show that PLK1 inhibitor synergizes with mTOR inhibitor to induce synergistic anti-tumor effect in colorectal cancer by antagonizing a compensatory Myc induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting Myc-associated tumorigenesis and therapeutic resistance.”


PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy

“Although 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to PI3K-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces Myc phosphorylation and protein accumulation. We show that PDK1-PLK1-Myc signaling is critical for cancer cell growth and survival and small molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting Myc-dependency. Intriguingly, PDK1-PLK1-Myc signaling induces an embryonic stem cell-like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self renewal. Finally, we show that PLK1 inhibitor synergizes with mTOR inhibitor to induce synergistic anti-tumor effect in colorectal cancer by antagonizing a compensatory Myc induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting Myc-associated tumorigenesis and therapeutic resistance.”


Myc-Driven Tumors Could be Next for Targeted Therapies

Scientists have made a breakthrough in inhibiting the tumor-driving protein myc, which previously had been impossible to target with drugs. Myc drives cells toward uncontrolled growth in tumors, and is involved in many of the most serious forms of cancer, including breast cancer, lung cancer, colorectal cancer, brain cancer, prostate cancer, and blood cancer. Scientists have found that one drug that indirectly targets myc slows tumor growth in a mouse model of myc-driven cancer. The key to the breakthrough was recognizing that myc relies partially on MTOR, another protein, for its protein supply. By targeting MTOR, the drug keeps myc from promoting tumor growth. The drug, called MLN0128, is already in clinical trials for a variety of cancers, but this is the first time it has been viewed as a tool to treat myc-driven cancer. The researchers said that other indirect targeted therapy drugs are already being tested in human studies to treat myc-driven tumors.


Myc-Driven Tumors Could be Next for Targeted Therapies

Scientists have made a breakthrough in inhibiting the tumor-driving protein myc, which previously had been impossible to target with drugs. Myc drives cells toward uncontrolled growth in tumors, and is involved in many of the most serious forms of cancer, including breast cancer, lung cancer, colorectal cancer, brain cancer, prostate cancer, and blood cancer. Scientists have found that one drug that indirectly targets myc slows tumor growth in a mouse model of myc-driven cancer. The key to the breakthrough was recognizing that myc relies partially on MTOR, another protein, for its protein supply. By targeting MTOR, the drug keeps myc from promoting tumor growth. The drug, called MLN0128, is already in clinical trials for a variety of cancers, but this is the first time it has been viewed as a tool to treat myc-driven cancer. The researchers said that other indirect targeted therapy drugs are already being tested in human studies to treat myc-driven tumors.