Cancer Stem Cells and How to Get Rid of Them


If you have not yet heard of cancer stem cells (CSCs), often considered to be the real culprits in cancer, it is about time you do. CSCs are stem cells found in tumors. Drugs that target them are showing promise in clinical trials. More on that later; first, let’s introduce the concept of stem cells:

All normal tissues in our bodies develop from a small number of very special cells known as stem cells. Stem cells can divide a seemingly unlimited number of times. Continue reading…


OncoMed Pharmaceuticals Announces Presentation of Tarextumab Small Cell Lung Cancer Data at the 16th World Conference on Lung Cancer

“OncoMed Pharmaceuticals Inc. (NASDAQ: OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported new biomarker and updated clinical data for the company’s Phase 2 anti-Notch2/3 therapeutic candidate, tarextumab (OMP-59R5). These data show the potential of Notch3 overexpression as a prognostic factor in small cell lung cancer and update OncoMed’s Phase 1b results for tarextumab in combination with standard-of-care chemotherapy for the first-line treatment of patients with extensive-stage disease. Anne Chiang, M.D., Ph.D., of the Yale School of Medicine, will present these data in a mini-oral presentation this afternoon at the 16th World Lung Conference on Lung Cancer.

” ‘Notch is known to be a fundamental cancer stem cell pathway driving the initiation and spread of tumors. Notch3 in particular has been associated with poor prognosis in a variety of solid tumor types, including pancreatic, breast and ovarian cancers,’ said Dr. Chiang. ‘Our analyses of small cell lung cancer patient tumors demonstrate that Notch3 overexpression in extensive-stage small cell lung cancer tumors is common and may be associated with poor survival. This is the first time that Notch3 tumor expression has been tested in small cell lung cancer and associated with poor patient outcomes.’ “


Lung Cancer Stem Cell Therapy to Be Trialled in UK

“British patients will be the first in the world to receive a pioneering cell therapy that scientists hope will transform the treatment of lung cancer.

“The treatment uses stem cells taken from bone marrow that have been genetically modified to find and destroy cancer cells.

“If successful, the treatment would offer hope to lung cancer patients, who continue to face one of the worst outlooks of all cancer patients. More than 40,000 people are diagnosed with the disease in the UK each year and only 5% of patients survive beyond 10 years.

“Prof Sam Janes, who is leading the research at University College hospital in London, said: ‘Cancers need something new. Chemotherapy works minimally and for a short while. This is truly experimental.’

“The trial, funded by the Medical Research Council, comes as a wave of cell-based therapies are making their way towards clinic. Early indications suggest these therapies could have a major impact on cure rates and survival times for patients.”


Disturbing Discovery: New Generation of Targeted Cancer Drugs Cause Tumors To Become Drug Resistant and More Aggressive

Breast-cancer-cell

“In a modest-sized lab at the Moores Cancer Center at the University of California, San Diego, scientists investigating how cancer cells develop resistance to drug treatments recently discovered something that surprised even the most seasoned members of the research team: A new generation of drugs that are currently among the most popular treatments for lung, breast and pancreatic cancers actually induce drug resistance and spur tumor growth.

“These popular cancer drugs, known as receptor tyrosine kinase inhibitors (RTKs), are actually making cancers stronger. That’s the bad news. The good news is that researchers believe they have found a way to eliminate that threat.

“Researchers found that two of the drugs — Erlotinib for lung cancer and Lapatinib for breast cancer — are effective for a while, but eventually stop killing cancer cells and begin prompting them to resist the drug and become more aggressive.

“ ‘We knew that cancer typically builds up a resistance to these and other drugs. But we did not know that these drugs actually induce tumor progression,’ said David Cheresh, Moores’ vice chair of pathology and the lead researcher on this study.”

Image: A breast cancer cell. London Research Institute EM Unit/Cancer Research UK


Prolonged Fasting 'Re-Boots' Immune System

“Results of a new study on mice and a phase 1 trial of humans suggest that prolonged cycles of fasting – for 2-4 days at a time – not only protect against toxic effects of chemotherapy, but also trigger stem cell regeneration of new immune cells and clearing out of old, damaged cells.

“The study, by researchers from the University of Southern California (USC) in Los Angeles, and published in the journalCell Stem Cell, is the first to show that a natural intervention can trigger regeneration of an organ or system through stem cells.

“The team believes the findings could benefit people with immune system damage, for example if they have received chemotherapy treatment for cancer. It could also benefit the elderly whose immune systems are weakened through aging, making them more susceptible to disease.”


Prolonged Fasting 'Re-Boots' Immune System

“Results of a new study on mice and a phase 1 trial of humans suggest that prolonged cycles of fasting – for 2-4 days at a time – not only protect against toxic effects of chemotherapy, but also trigger stem cell regeneration of new immune cells and clearing out of old, damaged cells.

“The study, by researchers from the University of Southern California (USC) in Los Angeles, and published in the journalCell Stem Cell, is the first to show that a natural intervention can trigger regeneration of an organ or system through stem cells.

“The team believes the findings could benefit people with immune system damage, for example if they have received chemotherapy treatment for cancer. It could also benefit the elderly whose immune systems are weakened through aging, making them more susceptible to disease.”


Prolonged Fasting 'Re-Boots' Immune System

“Results of a new study on mice and a phase 1 trial of humans suggest that prolonged cycles of fasting – for 2-4 days at a time – not only protect against toxic effects of chemotherapy, but also trigger stem cell regeneration of new immune cells and clearing out of old, damaged cells.

“The study, by researchers from the University of Southern California (USC) in Los Angeles, and published in the journalCell Stem Cell, is the first to show that a natural intervention can trigger regeneration of an organ or system through stem cells.

“The team believes the findings could benefit people with immune system damage, for example if they have received chemotherapy treatment for cancer. It could also benefit the elderly whose immune systems are weakened through aging, making them more susceptible to disease.”


HDAC Inhibitor Confers Radiosensitivity to Prostate Stem-Like Cells

“Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.”

 


An IKKα–E2F1–BMI1 Cascade Activated by Infiltrating B Cells Controls Prostate Regeneration and Tumor Recurrence

“Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα–BMI1 pathway is also activated in human PCa.”