Breast cancer drugs could help treat resistant lung cancers

A class of drugs used to treat certain breast cancers could help to tackle lung cancers that have become resistant to targeted therapies, suggests a new study in mice from the Francis Crick Institute and the Institute of Cancer Research (ICR).

The research, published in Cell Reports, found that lung tumours in mice caused by mutations in a gene called EGFR shrunk significantly when a protein called p110α was blocked.

Drugs to block p110α are currently showing promise in clinical trials against certain breast cancers, so could be approved for clinical use in the near future. The new findings suggest that these drugs could potentially benefit patients with EGFR-mutant lung cancers whose tumours have become resistant to treatment.

"At the moment, patients with EGFR-mutant lung cancers are given targeted treatments that are very effective for the first few years," explains study leader Professor Julian Downward, who has labs at the Crick and the ICR. "These drugs are improving, but unfortunately after a couple of years the cancer usually becomes resistant and starts to grow and spread again. The second line of treatment is currently conventional chemotherapy, which is not targeted and has substantial side-effects.Our new study suggests that it would be worth investigating whether p110α inhibitors could be used as a second-line therapy. As our research is at such an early stage, more research in mice and patient cells would be needed before even considering clinical trials, but it opens up a promising avenue of investigation."

For this research, the team targeted a specific interaction between the RAS protein and p110α. The RAS gene is mutated in around one in five cancers, causing uncontrolled growth, and is a key focus of Downward's research. When they blocked this interaction in genetically modified mice with EGFR mutations, their tumours shrank significantly.

Before the intervention, the tumours filled around two thirds of the space inside the lung. When the interaction between RAS and p110α was genetically blocked, this shrank significantly to about a tenth of the space inside the lung. The intervention also had very few side-effects.

"As we wanted to pinpoint the specific interaction responsible, we used a genetic technique that would not be practical in a patient treatment," says Downward. "We're looking to develop ways to do this with drugs, as blocking this specific pathway would significantly reduce side-effects, but this work is many years from the clinic. In the medium-term, investigating existing drugs that inhibit p110α will be the next step. While these have side-effects, including temporary diabetes-like symptoms during treatment, they are still less toxic than chemotherapy."

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New lung cancer guides aim to drive better outcomes and care

wo new, national guides that aim to drive better outcomes and care for all people affected by lung cancer were released by Cancer Australia. Lung cancer is the leading cause of death from cancer in Australia with an estimated 25 people dying every day from the disease in 2018.

All lung cancer patients, regardless of where they live, should have the benefit of the best care and have the best possible experience. These resources distill the essential elements of what that care should be and how to deliver it,” Dr Helen Zorbas, CEO Cancer Australia

Separate resources have been designed for health professionals and consumers, which share the goal of achieving optimal patient outcomes.

Delivering best practice lung cancer care for health professionals contains evidence-based, best practice information, strategies, tools and resources to support clinicians in providing consistent, high quality care for people affected by lung cancer.

I encourage all those involved in lung cancer care in Australia to implement and use these guides as part of a national coordinated effort to improve lung cancer outcomes.” Dr Zorbas

The resources build on the Lung Cancer Framework: Principles for Best Practice Lung Cancer Care in Australia, which support the uptake and use of the Principles for best practice care: patient-centred care; timely access to evidence-based pathways of care; multi-disciplinary care; coordination, communication and continuity of care; and data-driven improvements in lung cancer care.

To empower patients to actively participate in their own care, Getting the best advice and care, a guide for those affected by lung cancer provides information about what the principles will mean to them and what they can do better engage with health care professionals and make informed evidence-based decisions.

 

Dr Zorbas said the guides articulate the clear benefits to patients of implementing each of the principles –from improving survival to reducing anxiety and depression.

Releasing these resources during Lung Cancer Awareness Month serves as a timely reminder that anyone experiencing symptoms such as a persistent cough lasting 3 weeks or more, coughing up blood, a chest infection that won’t go away, or a changed cough should visit a doctor.

Although lung cancer mostly occurs in people over 60 years, it can affect people of any age, regardless of whether they smoke. It is estimated that in 2018, 12,741 people will be diagnosed with lung cancer in Australia.

The development of Lung Cancer Framework: Principles for Best Practice Lung Cancer Care in Australia and these new resources by Cancer Australia was guided by systematic and exacting reviews of the highest quality evidence and incorporates learnings and experiences from people affected by lung cancer. A national demonstration project was undertaken, along with consultation with health professionals and consumers, supported by Cancer Australia’s Lung Cancer Advisory Group.

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

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A grape constituent protects against cancer

Lung cancer is the deadliest form of cancer in the world, and 80% of death are related to smoking. In addition to tobacco control, effective chemoprevention strategies are therefore needed. A team of scientists from the University of Geneva (UNIGE), Switzerland, studied a well-known natural product, resveratrol, which is found in grapes and in red wine. While its chemopreventive properties against cancers affecting the digestive tract have been documented by previous studies, resveratrol has so far shown no effect on lung cancers. Thanks to nasal administration, the UNIGE team obtained very promising results in a study conducted in mice and described in the journal Scientific Reports.

"We tried to prevent lung cancer induced by a carcinogen found in cigarette smoke by using resveratrol, an already well-documented molecule, in a mouse model," explains Muriel Cuendet, Associate Professor, School of pharmaceutical sciences, UNIGE Faculty of Science.

This 26 week long study contained four groups of mice.

• The first one, the control, received neither carcinogen nor resveratrol treatment.
• The second received only the carcinogen.
• The third received both the carcinogen and the treatment.
• Fourth received only the treatment.

"We observed a 45% decrease in tumor load per mouse in the treated mice. They developed fewer tumors and of smaller size than untreated mice," says Muriel Cuendet. When comparing the two groups that were not exposed to carcinogen, 63% of the mice treated did not develop cancer, compared to only 12.5% of the untreated mice. "Resveratrol could therefore play a preventive role against lung cancer," she continues.

This formulation is applicable to humans

However, resveratrol does not seem suitable for preventing lung cancer: when ingested, it is metabolized and eliminated within minutes, and therefore does not have time to reach the lungs. "This is why our challenge was to find a formulation in which resveratrol could be solubilized in large quantities, even though it is poorly soluble in water, in order to allow nasal administration. This formulation, applicable to humans, allows the compound to reach the lungs," explains Aymeric Monteillier, scientist,School of pharmaceutical sciences of the UNIGE Faculty of Science.The resveratrol concentration obtained in the lungs after nasal administration of the formulation was 22 times higher than when taken orally. The chemoprevention mechanism is probably related to apoptosis, a process by which cells program their own death and from which cancer cells escape. The UNIGE research team will now focus on finding a biomarker that could contribute to the selection of people eligible for preventive treatment with resveratrol.

Towards a preventive treatment?

Resveratrol is an already well-known molecule, which is found in food supplements, meaning that no further toxicological study would be needed prior to commercialisation as a preventive treatment. "This discovery is unfortunately of little economic interest to pharmaceutical groups. The molecule is indeed simple and non-patentable and cancer prevention studies require a follow-up over many years," regrets Muriel Cuendet, without excluding the development of preventive treatment in humans..

 

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

New type of lung cancer

Researchers have discovered a new kind of small-cell lung cancer (SCLC). The discovery paves the way for developing personalized medicine approaches to target this previously unnoticed form of the disease.

"Cancer is not one thing, it's actually hundreds of distinct diseases." This common refrain helps explain the frustrating experience oncologists have in testing a promising new drug only to find that it works well in some patients but fails for the majority. Such experiences have led researchers to believe that the more they can distinguish tumor types based on meaningful biological signatures, the better chance they have of finding subsets of patients that will respond to specific drug candidates.

One type of cancer in desperate need of new drug is SCLC, a cancer without a specific treatment that often spreads early. Chemotherapy, radiotherapy, and surgery enable only 6% of patients to survive 5 years from the time of their diagnosis. About 10%-15% of all lung cancers are SCLC.

Fresh insight comes from an analysis of gene activity in human SCLC tumors. It reveals an unexpected activity pattern in around 20% of samples. The research team, led by Dr. Christopher Vakoc, Cold Spring Harbor Laboratory (CSHL) found a paucity of neuroendocrine markers in pulmonary neuroendocrine cells, a cell type thought to be the source of SCLC.

They used a method that was developed in 2015 that employs the gene-editing tool CRISPR to screen for specific proteins that are critical to the growth of various human cancer cell lines, including SCLC lines. Using this "CRISPR screen," the team found that a transcription factor called POU2F3 is expressed exclusively in the minority of SCLC tumors with low levels of neuroendocrine markers. It turns out that this variant form of SCLC tumors are derived from a separate class of rare cells called tuft cells.

"We were using the CRISPR screen to discover new vulnerabilities in this disease that we didn't know about before."The surprise is that in the process, we discovered a new form of lung cancer. " says Dr.Vakoc

Developing drugs that specifically target the function of POU2F3 may be particularly effective in the subset of patients with tumors that express high levels of this transcription factor.

"In the past, we've lumped the different forms of SCLC together because they look similar on a microscope slide, but we now have some molecular tests that can easily discriminate these malignancies. Our findings suggest that we should be designing clinical studies for them separately, to find therapies that might cater to the different types of tumor. " says Dr.Yu-Han Huang

Researchers is currently looking for collaborators to do preclinical tests in mice to test compounds that target POU2F3. They also plan to use their CRISPR-based stress test to look for variant types of pancreas cancer which they hope might provide similarly specific targets for treatments.

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