Curinggenetics

LKB1 (STK11) company

Repurposing FDA approved drugs for efficiency, speed, and cost effectiveness.

Diversified Scopes of Work (SOW) build on previous R&D efforts for identification of new candidate therapies to quickly commence clinical trials. Many agents approved for other uses have already been tested in humans, so detailed information is available on their pharmacology, formulation, and potential toxicity.

SOW1 (human phase)

Ruxolitinib, a Jak 1/2 inhibitor, significantly reduced tumorigenesis in a PJS mouse model. Based on the Inventors' preclinical results, they expect Ruxolitinib to also reduce tumorigenesis in PJS patients. Other Jak inhibitors such as Itacitinib are also being engaged to reduce or stop polyposis and tumorigenesis.

SOW2 (human phase)

Rapamycin (Sirolimus), an mTOR inhibitor, is a promising candidate in treatment and prevention of PJS polyps. PJS is caused by mutation of LKB1 gene which leads to increased activity of mTOR pathway.

SOW3

Combo approach. Use the identified FDA approved compounds with Rapa and the mutation in cell lines and or animal models for treatment and repurposing.

PJS Animal model proof

Polyps are reduced and eliminated in ruxolitinib treated LKB1 knockout mice.

SOW4

Utilize mRNA approach. Intestine delivery pill identified. Develop a vaccine to recognize the mutation and stop formation of polyps. Checkpoint immunotherapy may also be considered as a combo therapy.

SOW5

Stem cell therapy. Infuse corrected or donated stem cells to be proliferated as healthy T cells to supplement protein and correct deficiencies.

SOW6

Gene therapy and editing. Repair mutated LKB1/STK11 tumor suppressor gene.

SOW7

Liquid Biopsy. Lessen the burden of ongoing intensive screening and risks for patients.

Precision Medicine paving the way for a new era

Over the past few years, a number of products that signal a new era of medical research and development have entered the markets and are on the horizon.

Molecular Mechanism that underlie LKB1

Germline mutations of the LKB1 tumor suppressor gene result in Peutz–Jeghers Syndrome (PJS) characterized by intestinal hamartomas and increased incidence of epithelial cancers.

Restoration of silenced PJS gene, LKB1

Germline mutations of the LKB1 tumor suppressor gene lead to Peutz-Jeghers Syndrome (PJS) with a predisposition to cancer.

Therapeutic knock when LKB1 inactivated

LKB1 is commonly thought of as a tumor suppressor gene because its hereditary mutation is responsible for cancer syndrome, and somatic inactivation of LKB1 is found in non-small cell lung cancer, melanoma, and cervical cancers.

LKB1 is mutated in PJS and variety of cancers

Increasing evidence has highlighted that deficiency of LKB1 in cancer cells induces extensive metabolic alterations that promote tumorigenesis and development.

Targeting the LKB1 Tumor Suppressor

Physiologically, LKB1 possesses multiple cellular functions in the regulation of cell bioenergetics metabolism, cell cycle arrest, embryo development, cell polarity, and apoptosis.

Cancer immunotherapy via dendritic cells

The molecular identification of human cancer antigens has allowed the development of antigen-specific immunotherapy.

Genome editing with Cas9 corrects mice mutation

We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia.

LKB1 and PAR-4

The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo.

P53

The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.

Autophagy & LKB1

Does autophagy take a front seat in lifespan extension?

Epigenetic changes in pediatric solid tumors

Somatic mutations or deregulated expression of chromatin modifying enzymes are being identified at high frequency.

LKB1 & Embryonic Stem Cells

Human embryonic stem cells maintained on human amniotic epithelial cells (hESCshAEC) are better preserved in an undifferentiated state and...

Epigenetics targeting solid tumors

Epigenetic therapies may play a prominent role in the future management of solid tumors.

LKB1 tumor suppressor & Lung cancer

To stop lung cancer from spreading, researchers target a specific gene. By Adam Marcus, PhD

LKB1/STK11 & Lung cancer

Gene discovery may stop the spread of lung cancer.

By Reuben Shaw, PhD

Precision Medicine

Precision medicine when every cancer is personal.

By Adam Marcus, PhD

Ability to identify cancerous genes

Research focused on the relative importance of selection of genomic instability. By Ian Tomlinson, PhD

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