Amplification of and oncogenic mutations in ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2-amplified or -mutant lung cancers. We show that cotreatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy.

Summary:

Over the last two decades HER2 aberrations have been thoroughly investigated as potential therapeutic targets in advanced non–small cell lung cancer, with relatively modest results. Two articles published in this issue of Cancer Discovery further expand the knowledge on therapeutic exploitation of HER2 in lung cancer, addressing a large unmet medical need.

See related article by Li et al., p. 674.

See related article by Tsurutani et al., p. 688.

Low-dose adjuvant epigenetic therapy (AET) reduced metastasis and promoted survival in mouse models.

Background:

Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population.

Background:

Colonoscopy follow-up recommendations depend on the presence or absence of polyps, and if found, their number, size, and histology. Patients may be responsible for conveying results between primary and specialty care or providing medical information to family members; thus, accurate reporting is critical. This analysis assessed the accuracy of self-reported colonoscopy findings.

Với những ngôi nhà có trần cao và gác lửng, bạn hoàn toàn có thể bố trí một phòng ngủ tiện nghi trên gác lửng, vừa tối ưu hóa không gian, vừa khiến ngôi nhà thêm phong cách, cá tính.

Trang hoàng sân vườn không phải lúc nào cũng tốn công và đắt đỏ. Chỉ với những chiếc đèn phong cách Rustic mộc mạc, bạn sẽ dễ dàng “hô biến” góc sân và khu vườn nhỏ của mình thành chốn lung linh huyền ảo cho những bữa tiệc ngoài trời.

Tôi muốn xây nhà cấp 4 có gác lửng, 2 phòng ngủ, 1 WC, 1 khu bếp, phòng khách và ăn chung. Nhà hướng Bắc. Tôi mạng Tây tứ trạch, phong thủy hợp lý, báo giá trọn gói chìa khóa trao tay.

On Tuesday the president took his first trip since the coronavirus grounded the country, to a Honeywell factory in battleground state Arizona. This particular Honeywell factory produces N95 masks. Pictures of the trip immediately surfaced on the internet, and they showed a president sporting his usual mango-tinted, ever-tan skin, his usual topiary-structured hair tinted a baffling yellowish, and a pair of clear safety goggles.

But what was missing? What we did not see on the president’s face was a mask. While the rest of us cover our faces as recommended by the CDC, the president does not. In fact, we have never seen a mask on the president, despite the president’s love of masking himself when it comes to his tax returns, his sexual assault allegations, and his financial dealings.   

On Wednesday, when pressed on his decision not to wear a mask at a mask factory, the president responded with the very fishy, “I had a mask on for a period of time, I had it on back, backstage. But they said you didn’t need it, so, I didn’t need it. And by the way, if you noticed, nobody else had it on that was in the group.” Okay. Whatever you say. 

Read more at The Daily Beast.

The plunge in jobs was 73,800 relative to February, but Saskatchewan saw a shallower decline than any other province as COVID-19 devastates labour markets across Canada.

A week packed with U.S. economic data is likely to provide investors with more evidence of the extent to which the coronavirus pandemic has hit growth, sharpening the debate on whether a rebound in stocks has been justified amid an unprecedented slowdown.

Oil prices in the US have dropped into negative territory due to collapse in demand amid the coronavirus pandemic.

John Lewis sales have plunged, despite a surge in online orders, after it was forced to shut stores in face of coronavirus.

A one-year-old girl with chronic lung disease and a heart defect has become one of the UK's youngest coronavirus survivors.

Britain's weather woes are set to continue with wet and windy conditions expected to last all week.

Rain will batter all four corners of the country for periods on both Saturday and Sunday and temperatures will plummet following the sunniest ever April.

A five-year-old child has been taken to hospital after falling out of a window in north London.

In the late afternoon session, the scrip was being traded at 20.61 pounds, down by 5.50 per cent on the LSE. Vedanta opened on a positive note, but soon swung into the red.

Vietnam Airlines pilot one of only two serious cases in country with mass testing regime

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A 43-year-old British man may undergo a lung transplant in Vietnam, where he is critically ill with Covid-19.

The man, a Vietnam Airlines pilot, developed a fever and cough on 17 March, and was later admitted to Ho Chi Minh City Hospital for Tropical Diseases.

Court documents provide insight into the shambolic and costly planning issues being created by a major housing expansion on the southern outskirts of Sydney.

With call centers in India, the Philippines and elsewhere shut down for the coronavirus, many robocall companies have simply stopped making calls.

Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 may be nonspecific, some characteristic imaging findings are emerging, says the American Journal of Roentgenology (AJR). Careful evaluation of the distribution, lung zone preference, and symmetry of the abnormalities with an eye for a few unique differentiating imaging features can allow radiologists to offer a narrower differential diagnosis in pediatric patients, leading to optimal patient care.

Douglas Moore, who also has a lung condition, received a round of applause as he was discharged from Kettering General Hospital.

The major miners, energy and bank stocks led heavy selling on the Australian share market, which closed 5 per cent lower as selling accelerated in late trade.

The Australian share market closes higher, shaking off initial falls, while Afterpay shares surge after revealing investment by Chinese firm Tencent. Job ads fell by 50 per cent in April as coronavirus hit businesses.

Artificial intelligence technology is being rapidly deployed worldwide to help tackle Covid-19.

As cancer research reveals the genetic basis of the disease, pharmaceutical companies are pursuing targeted therapies that address certain groups of patients. One such drug from Novartis won FDA approval Wednesday, making it the first therapy cleared by the agency to treat patients whose non-small cell lung cancer (NSCLC) carries a certain genetic mutation. The […]

A Phase 3 study of Sanofi and Regeneron’s Libtayo (cemiplimab) as a monotherapy for advanced or metastatic non-small cell lung cancer (NSCLC) has been stopped early after showing strong overall survival benefit, it has emerged.

The FDA has awarded marketing authorisation to Novartis for the Oral MET inhibitor Tabrecta for the first-line treatment of metastatic non-small cell lung cancer in patients whose tumors have a mutation that leads to MET exon 14 skipping (METex14), regardless of whether they have previously received any type of treatment.

A multi-year collaboration between China’s Innovent Biologics and USA-based Eli Lilly is bearing fruit,…

Late Wednesday, the US Food and Drug Administration said it has granted accelerated approved for Tabrecta…

The US Food and Drug Administration has granted accelerated approval for Retevmo (selpercatinib) capsules…

- Libtayo decreased the risk of death by 32.4% compared to chemotherapy

You can't blame them for trying: With the White House set to change hands in less than a year's time - likely bringing on board a more eco-friendly administration - industry groups have been pressing the EPA to squelch stricter air-quality standards

Authors of a new study say dogs may help develop over-the-counter tests capable of life-saving early detection.

Laura Dern, Kellie Pickler, Valerie Harper Among Notable Voices Kicking Off National Women’s Lung Health Week

2nd Annual Women’s Lung Health Barometer Animated Video

The Conference Board said Tuesday that its confidence index tumbled to a reading of 86.9, the lowest level in nearly six years and down from 118.8 in March.

The coronavirus crisis actually caused consumer health-care spending to plunge 18% in Q1.

U.S. consumer spending plunged 7.5% in March, reflecting the growing impact of the coronavirus pandemic as Americans complied with stay-at-home orders.

At a time of short-term market panic about the coronavirus, Warren Buffett offers a new lesson on how to identify long-term stock winners. The key: a focus on corporate reinvestment.

Exxon Mobil reported a loss in the first quarter as oil prices dropped to historic lows.