Tag: lung cancer

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Why Some Lung Cancer Patients Stop Responding to Treatment

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Anatomical model of lungs
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Published in Cancer Research, researchers have discovered why some patients with nonsmall cell lung cancer stop responding to treatment with tyrosine kinase inhibitors (TKIs): an epigenetic switch is flipped, reactivating genes that inhibit the effect of these drugs.

TKIs, specifically epidermal growth factor receptor inhibitors, are typically used to treat people with nonsmall cell lung cancer, a prevalent and usually incurable type of cancer that accounts for 80–85% of lung cancers. About 15–20% of these patients will become resistant to these standard treatments, resulting in their eventual death. This is because the cells develop a mutation that leads to resistance. But about half of the remaining resistant patients remain unexplained. 

Cellular biologist Andrea Kasinski and her lab have found that the cause involves epigenetics. When cells lose a histone called methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors. This could open up development of new therapeutics and gives researchers and doctors a deeper insight into the biology and progression of cancers, especially the role that epigenetic-modifying proteins play in drug resistance, a poorly understood phenomenon.

“For the majority of genes that contribute to cancer, we’re not sure how they work yet,” Kasinski said. “And for many, we don’t have a way to therapeutically target them. Research like this, that helps us understand how those genes work to determine cancer outcomes, adds to our understanding of the network. This knowledge will ultimately lead us to better therapeutics.”

Source: Purdue University

Categories : CancerTags :

How Lung Cells Stave off Lung Cancer in Smokers

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Cigarette smoking
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Even though cigarette smoking is by far the main cause of lung cancer, only a minority of smokers develop the disease. A study reported in Nature Genetics suggests that some smokers may have robust mechanisms that protect them from lung cancer by keeping mutations in check. The findings could help identify those smokers who face an increased risk for the disease and therefore warrant especially close monitoring.

“This may prove to be an important step toward the prevention and early detection of lung cancer risk and away from the current herculean efforts needed to battle late-stage disease, where the majority of health expenditures and misery occur,” said Simon Spivack, MD, MPH, a co-senior author of the study.

For a long time, it has been assumed that smoking leads to lung cancer by triggering DNA mutations in normal lung cells. “But that could never be proven until our study, since there was no way to accurately quantify mutations in normal cells,” said Dr Jan Vijg, a study co-senior author. Dr Vijg overcame that obstacle a few years ago by developing an improved method for sequencing the entire genomes of individual cells.

Single-cell whole-genome sequencing methods can inadvertently introduce sequencing errors difficult to distinguish from true mutations – a major flaw when looking for rare and random mutations. To get around this, Dr Vijg developed a sequencing technique called single-cell multiple displacement amplification (SCMDA). 

The researchers used SCMDA to compare the mutational landscape of normal lung epithelial cells from two types of people: 14 never-smokers, ages 11 to 86; and 19 smokers, ages 44 to 81, who had smoked a maximum of 116 pack-years. (One pack-year of smoking equals 1 pack of cigarettes smoked per day for one year.) The cells were collected from patients who were undergoing bronchoscopy for diagnostic tests unrelated to cancer. “These lung cells survive for years, even decades, and thus can accumulate mutations with both age and smoking,” said Dr Spivack. “Of all the lung’s cell types, these are among the most likely to become cancerous.”

The researchers found that mutations accumulated in the lung cells of non-smokers as they age, and significantly more mutations were found in the lung cells of the smokers. “This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesised,” said Dr Spivack. “This is likely one reason why so few non-smokers get lung cancer, while 10% to 20% of lifelong smokers do.”
The study also revealed that the number of cell mutations detected in lung cells increased in a straight line with the number of pack years of smoking and, presumably, so did the lung cancer risk. However, the cell mutations stopped rising after 23 pack-years of exposure.

“The heaviest smokers did not have the highest mutation burden,” said Dr Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation. This leveling off of mutations could stem from these people having very proficient systems for repairing DNA damage or detoxifying cigarette smoke.”

The finding has led to a new research direction. “We now wish to develop new assays that can measure someone’s capacity for DNA repair or detoxification, which could offer a new way to assess one’s risk for lung cancer,” said Dr Vijg.

Source: Albert Einstein College of Medicine

Categories : CancerTags :

Unmet Lung Cancer Patient Needs Have a Significant Impact

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Research studies suggest that unmet physical and psychological needs of patients with lung cancer have a significant impact on patients’ quality of life and affect their ability to continue with everyday activities. 

Lung cancer is the leading cause of cancer death in the United States. No specific signs and symptoms exist for lung cancer, and most patients already have advanced disease at the time of presentation. In a study published in the European Journal of Cancer Care, researchers examined the impact of unmet needs on patients’ lives.

Analysing results from six studies involving 562 patients, researchers found that almost two thirds of the patients had been diagnosed with advanced cancer (stage III or IV), and most had been diagnosed for less than two years. There was a negative association between quality of life and unmet needs using two different measures. In two of the studies, the relationship was limited to physical and/or psychological needs.

In the physical domain, lack of energy and tiredness were common unmet needs, and uncertainty about the future, fears, and worry were among the most common in the psychological domain.

“This research underscores the high burden of unmet needs for individuals with lung cancer, often resulting from late diagnosis and associated lack of curative treatment,” said corresponding author Simon Dunne, PhD, of Dublin City University, in Ireland. “There is a need for early intervention and tailoring of pre-existing services to address unmet supportive care needs in this cancer group.”

Source: Wiley

Categories : CancerTags :

Investigation of Cannabidiol Oil for Lung Cancer Suggested

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In BMJ Case Reports, doctors suggest investigating the use of cannabidiol (‘CBD’) oil as a potential lung cancer treatment, after dealing with a daily user whose lung tumour shrank in the absence of conventional treatment.

The body’s own endocannabinoids are involved in various processes, including nerve function, emotion, energy metabolism, pain and inflammation, sleep and immune function.

Cannabinoids are chemically similar to these, and can interact with signalling pathways in cells, including cancer cells. While they have been studied for use as a primary cancer treatment, there have been inconsistent results.

Despite treatment advances, survival rates for non-small cell lung cancer remain low at around 15% five years after diagnosis, with average survival without treatment is about seven months.

The authors describe the case of a woman in her 80s, a pack-a-week smoker diagnosed with non-small cell lung cancer. The woman also had mild chronic obstructive pulmonary disease (COPD), osteoarthritis, and hypertension, for which she was taking various drugs.

Her tumor was 41 mm in size at diagnosis, with no evidence of local or further spread, so was suitable for conventional treatment of surgery, chemotherapy, and radiotherapy. But the woman refused treatment, so was placed under ‘watch and wait’ monitoring, which included regular CT scans every 3-6 months.

These showed that the tumor was progressively shrinking, reducing in size from 41 mm in June 2018 to 10 mm by February 2021, equal to an overall 76% reduction in maximum diameter, averaging 2.4% a month, say the report authors.

When contacted in 2019 to discuss her progress, the woman revealed that she had been taking CBD oil as an alternative self-treatment for her lung cancer since August 2018, shortly after her original diagnosis.

She had done so on the advice of a relative, after witnessing her husband struggle with the side effects of radiotherapy. She reported consistently taking 0.5 ml of the oil, two to three times a day.

According to the supplier, the main active ingredients were Δ9-­tetrahydrocannabinol (THC) at 19.5%, cannabidiol at around 20%, and tetrahydrocannabinolic acid (THCA) at around 24%.

The supplier also said that she should avoid hot food or drinks when taking the oil as she might otherwise feel stoned. The woman reported reduced appetite since taking the oil but had no other obvious ‘side effects’. There were no other changes to her prescribed medications, diet, or lifestyle, and she continued smoking throughout.

The authors cautioned that this is just one case report, with only one other similar case reported, and it is unclear which of the CBD oil ingredients might have been helpful.

“We are unable to confirm the full ingredients of the CBD oil that the patient was taking or to provide information on which of the ingredient(s) may be contributing to the observed tumour regression,” they pointed out.

They further emphasised that, “although there appears to be a relationship between the intake of CBD oil and the observed tumuor regression, we are unable to conclusively confirm that the tumor regression is due to the patient taking CBD oil.”

The authors concluded that, “more research is needed to identify the actual mechanism of action, administration pathways, safe dosages, its effects on different types of cancer and any potential adverse side effects when using cannabinoids.”

Source: News-Medical.Net

Categories : Ageing CancerTags :

Older Patients with Advanced Lung Cancer Suffer Reduced Mobility

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New research found that older patients with non-small cell lung cancer often have low life-space mobility prior to starting lung cancer treatment. Life-space mobility is the ability to move within one’s environment from the home to the wider community. The findings were published in the Journal of the American Geriatrics Society.

The study recruited 93 patients aged 65 to 94 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. 

The Life-Space Assessment scores had a range of 0 to 120, with a score under 60 being considered restricted. The researchers found that the average pretreatment score was 67. On average, the score fell by 10 points from pretreatment to one month after treatment started and remained low at six months.  

The decline at one month was greater among patients with high anxiety. On the other hand, a lower body mass index prior to starting treatment was associated with an improvement in the score during treatment.  

“Life-space mobility is a well-studied patient-centered outcome in general aging research but is only now being examined for older adults with cancer,” said lead author Melisa L. Wong, MD, MAS, of the University of California, San Francisco. “Our study’s novel design provided a unique lens into how quantitative changes in life-space mobility are experienced qualitatively by older adults with lung cancer.”

Source: Wiley

Categories : Cancer Medical Research & TechnologyTags :

Plant Virus-based Treatment Protects Against Lung Tumours

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Image source: CDC/Unsplash

Using a virus that grows in black-eyed pea plants, nanoengineers developed a new treatment that could keep metastatic cancers at bay from the lungs. 

Not only did the treatment slow tumour growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimised the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published in Advanced Science.

Researchers developed an experimental treatment that combats metastatic spread. This involves a plant virus called the cowpea mosaic virus, harmless to animals and humans, but which the body still registers as a foreign invader, thus triggering an immune response that could also boost the body’s cancer-fighting ability.

The idea is to use the plant virus to help the body’s immune system recognise and destroy cancer cells in the lungs. The virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at the University of California San Diego.

To draw this immune response to lung tumours, Prof Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection in the lungs. Overexpression of S100A9 has been observed to play a role in tumour growth and spread.

“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Prof Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”

“Because these nanoparticles tend to localise in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering PhD student in Steinmetz’s lab who is one of the co-first authors on the paper.

To make the nanoparticles, the researchers infected black-eyed pea plants with cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then fixed S100A9-targeting molecules to the particles’ surfaces.

The researchers performed both prevention and treatment studies. In the prevention studies, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells into these mice. Treated mice showed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.

In the treatment studies, the researchers administered the nanoparticles to mice with metastatic tumours in their lungs. The treated mice exhibited smaller lung tumours and survived longer than untreated mice.

Prof Steinmetz envisions that the treatment could be useful after tumourectomy. “It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumours. Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis,” she said.

More detailed immunotoxicity and pharmacology studies are needed before this can progress to a treatment. Future studies will also explore combining this with standard cancer therapies such as chemotherapy.

Source: University of California – San Diego

Categories : Cancer Ethics and LawTags :

Many Lung Cancer Patients Choose Euthanasia Without Exploring Treatment

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A Canadian study of lung cancer patients who opted for “medical assistance in dying” often proceeded without consultation with their radiation oncologist or medical oncologist.

In a Canadian study of 45 individuals diagnosed with lung cancer who used medical assistance in dying (also known as physician-assisted suicide), about 20% did not have a radiation oncologist involved when making the decision and 22% did not have a consultation with a medical oncologist, said Sara Moore, MD, of Ottawa Hospital Research Institute of the University of Ottawa.

Since 2016, about 60% of those seeking to end their life through legal means introduced in Canada had been diagnosed with cancer, Dr Moore explained in a presentation at the virtual World Conference on Lung Cancer.

Driven by loss of autonomy, control and dignity
The designated discussant, Monica Malec, MD, a geriatric and palliative care physician at the University of Chicago, said this was the first study to evaluate medical assistance in dying in patients with lung cancer, oncologists’ involvement, and treatment history.

“The demand for medical assistance in dying is increasing and is becoming more readily available to patients,” Dr Malec said. “Patients are seeking this option despite the availability of more effective and more tolerable treatment options. Existing literature suggests that loss of autonomy, control, and dignity are the primary drivers for seeking medical assistance in dying rather than uncontrolled symptoms, and the decision to pursue medical assistance in dying may occur pre-illness.”

Moore noted that while lung cancer accounts for 20%-25% of all cancer deaths overall, in the current study 17.5% of the patients had lung cancer diagnoses. “Lung cancer comprises slightly fewer medical assistance in dying cases than expected compared to lung cancer death rates,” she said.

Improved treatments disregarded
“Biomarker-driven targeted therapy and immunotherapy offer effective and tolerable new treatments, but a subset of patients undergo medical assistance in dying without accessing — or, in some cases, without being assessed for — these treatment options,” Dr Moore continued. “Most patients were assessed by an oncology specialist, though less than half received systemic therapy.”

“Given the growing number of efficacious and well-tolerated treatment options in lung cancer, consultation with an oncologist may be reasonable to consider for all patients with lung cancer who request medical assistance in dying,” she said.

The researchers screened data from the Ottawa region, and identified 256 patients with a cancer diagnosis who had used medical assistance in dying. Of these, 45 patients had a lung cancer diagnosis.About 85% had a history of tobacco smoking, and 36% were current smokers at the time they sought medical assistance in dying, Moore reported. Thirteen of these patients had no biopsy confirmation of their disease, but almost all (91%) opting for medical assistance in dying were diagnosed with metastatic disease. Average age was 72 years, and 64% (29 of 45 patients) were women, even though men are more often diagnosed with lung cancer, Dr Moore noted. 
Limitations included being limited to only a single region, and a lack of information on patients’ decision-making process.

Source: MedPage Today

Categories : CancerTags :

Pre-op Immune Checkpoint Inhibition in Lung Cancer

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According to a prospective multicenter trial, one fifth of patients with operable early-stage non-small cell lung cancer (NSCLC) had major pathologic responses (MPR) and over 40% had pathologic downstaging after neoadjuvant atezolizumab.

Out of 144 patients, 30 achieved MPR (defined as ≤10% viable tumour cells), 10 of whom had pathologic complete response (pCR), while 66 experienced downstaging and upstaging occurred in 29. 

Jay M Lee, MD, of the David Geffen School of Medicine at the University of California Los Angeles, explained: “The LCMC (Lung Cancer Mutation Consortium)3 study successfully met its primary endpoint of achieving major pathologic response in 21% of patients, and a pathologic complete response rate of 7%. Neoadjuvant atezolizumab monotherapy was well tolerated, with no new safety signals, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window, with a short time frame from completion of atezolizumab and with a corresponding high R0, or complete resection rate.”

Some 90% of patients were still alive at 18 months, and 80% were disease-free and alive. The findings indicate that neoadjuvant therapy with an immune checkpoint inhibitor (ICI) is possible thought it does make surgery harder, said invited discussant Shinichi Toyooka, MD, of Okayama University Hospital. Similar outcomes were seen in patients with stage I-II versus stage III disease, although survival data is currently lacking, requiring follow-up to find out if single-agent ICI is sufficient for all patients with operable NSCLC.

“I think single ICI can be used for early-stage disease and poor performance status,” said Toyooka. “On the other hand, a combination of ICI and chemotherapy is suitable for advanced-but-resectable cases.”

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy. Lee said 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

The trial included 181 patients with newly diagnosed, resectable stage Ib-IIIa and selected IIIb (T4 because of mediastinal invasion) NSCLC and no targetable mutations, of which 159 underwent surgery. 15 patients were later found to have EGFR/ALK-positive disease and excluded from analysis. Patients had radiographic staging before and after two cycles of atezolizumab and then underwent surgery within 30 to 50 days after finishing neoadjuvant therapy.

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy; 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

Source:MedPage Today

Presentation reference: Lee JM, et al “Surgical and clinical outcomes with neoadjuvant atezolizumab in resectable stage Ib-IIIb NSCLC: LCMC3 trial primary analysis” WCLC 2020; Abstract PS01-05.