Published On: Fri, Apr 6th, 2018

Scientists find two combo drugs that kill lung cancer

There is hope for lung cancer sufferers worldwide. A breakthrough research has found that  the use of two existing drugs could successfully treat the disease. The study delves deep into the molecular survival kit of lung tumours.

Understanding how lung tumours survive and grow leads to an innovative new treatment.

Many cancer deaths are driven by the KRAS oncogene. KRAS is an essential gene, but in its mutant form, it is an important step in the generation of many types of cancer.

For over 30 years, the KRAS oncogene has been a focus of research. Finding a way to remove its teeth would be pivotal in the treatment of a range of cancers.

As part of this effort, rather than targeting the gene directly, some scientists have focused on pathways that are related to the errant gene.

One pathway of interest centres on insulin and insulin-like growth factor-1 (IGF-1). This pathway helps to regulate the uptake of nutrients into the cell, providing it with the energy and raw ingredients it needs to grow.

If the tumour cell’s fuel supply could be severed, its onward march might be halted. However, it is not clear whether KRAS oncogenes are reliant on this particular pathway, and, in clinical trials, results have not been encouraging.

In fact, one study in mice found that lung tumours actually became more aggressive after the pathway was suppressed.

Attacking KRAS-related pathways

Undeterred, a team from the Boston Children’s Hospital in Massachusetts used a fresh approach. In the mouse study mentioned above, the insulin/IGF-1 signalling pathway was only partially closed off. In the latest study, though, a genetic technique was used that shut it down entirely.

To do this, the scientists crossed two strains of genetically modified mice. The first is a well-used model for KRAS-driven lung cancer, and the other is a mouse used to study diabetes that lacks insulin/IGF-1 signalling.

In the diabetes mouse model, the insulin/IGF-1 pathway is unshackled by the deletion of two genes: Irs1 and Irs2. These encode “adaptor” proteins, which are essential for the smooth running of the insulin/IGF-1 pathway.

“Our study uses a robust way to block insulin/IGF-1 signalling and addresses a long-standing question in KRAS-mutant lung cancer. When you use genetics, results can be more conclusive,” said senior study author Nada Kalaany, Ph.D, an assistant professor at Harvard Medical School, Boston, MA

Using their new model, the scientists demonstrated that by suppressing the two adaptor proteins, insulin/IGF-1 signalling is blocked and lung tumours are significantly suppressed:

“Almost all animals in this lung cancer model typically die within 15 weeks of KRAS activation,” says Kalaany. “But, the ones that lost both Irs1 and Irs2 were completely fine — we saw almost no tumours at 10 to 15 weeks.”

This finding is important because drugs that block insulin/IGF-1 signalling are already in use and freely available.

The results are published this week in the Proceedings of the National Academy of Sciences. While the preliminary findings are hopeful, the researchers knew that there was more work to be done; cancer is a complex, ever-morphing disease with a terrifying knack for circumventing medical interventions.

Outfoxing lung cancer

To observe whether the cancer cells were able to navigate around this new roadblock, the team let the animals live longer to see what happened next.

As Kalaany explains, “Sure enough, at around 16 weeks, we started seeing some tumours. So, then we asked, how were these tumour cells able to overcome loss of Irs1 and Irs2?”

The answer was found in the levels of essential cellular building blocks: amino acids. Tumour cells lacking the adaptor proteins failed to move amino acids into their cells, despite a plentiful supply outside of the cell.

“Growth factors, like IGF-1, tell cells that nutrients are around,” says Kalaany, “so when you suppress their signalling, the tumour cells don’t take up the amino acids and think they are starved.”

“But we found that the tumour cells can compensate for this and break down their own proteins to generate amino acids.”

So, the KRAS-driven tumours threw out a curve ball: they had, once again, figured out a workaround. By breaking themselves down — in a process known as autophagy — they can generate the raw material they need to thrive.

The researchers, however, were one step ahead.

Heading cancer off at the pass

Drugs that inhibit protein breakdown are already available. These include chloroquine, which is currently involved in a number of cancer drug trials, and bortezomib, which blocks proteasomes (protein-digesting structures) and is already used to treat myeloma.

When the two prongs of the attack were combined, the results were more than encouraging. They found that tumour cells lacking Irs1 and Irs2 did not grow well, and, when the inhibitors were added, growth stopped almost completely.

Additional studies will now be needed to understand how these two drug types might interact in a patient. However, this is a considerable breakthrough, and the researchers are excited to take it to the next phase.

“Our work tries to identify metabolic dependencies and vulnerabilities in tumours,” says Kalaany. “If we identify collaborators, we would love to have a clinical trial in non-small-cell lung cancer combining IGF-1 inhibitors with autophagy inhibitors or proteasome inhibitors.”

By testing to breaking point every part of a tumour cell’s survival kit, researchers will, one day, beat cancer.

Reported by Tim Newman for Medical News Today

© 2018, Hallmarknews. All rights reserved. Reference and link to this site is required if you wish to reuse any article.

Reactions from Facebook

comments and opinions

Leave a comment

XHTML: You can use these html tags: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

Most Shared

Recent posts

  • Saraki to Nigerian youths: Turn your cellphones into business tools

    President of the Senate, Dr. Abubakar Bukola Saraki, on Sunday called on the nation’s youths to venture into entrepreneurship through their cell-phones as a way of self-employment and creating job opportunities for others. Saraki gave the charge while delivering the Fourth Convocation Lecture of the Adeleke University, Ede in the State of Osun, on Sunday. […]

  • Gov. commends Abiriba entrepreneurship drive

    From PETER OKORE, Umuahia   Historically, one of the towns that has often been associated with merchandise, entrepreneurship and self-help development efforts in Nigeria is Abiriba; a clan in Ohafia Local Government Area of Abia state. The town, popularly called, “small London” became famous for its age-long endeavours since the era of the British military expedition of Igboland,(1830-1930) in former Eastern Region of […]

  • Population crisis: Nigeria Analysts raise Alarm

    Against increasing concerns about exploding population figures, Nigerian economists, in growing numbers, are raising their voices over an impending tragedy if the current growth rate of 3 per cent per annum is not flipped back. Available data lays bare Nigeria’s romance with disaster. Recent IMF statistics puts Nigeria’s population at a stumping 199.5 million people […]

  • Shareholders bemoan Oando’s deepening crises

    –as court orders top executives to pay N245 billion By OKEY ONYENWEAKU It seems the woes of oil producing and marketing company, Oando Plc, will never end. Just smarting from the problems and controversy that almost brought the firm to its knees over book cooking, another more pernicious headache is breaking out; this time court […]

  • Top banks battle rising NPLs; 2 lose top rating

    By FELIX OLOYEDE In the face of daunting economic challenges commercial lending institutions called Systemically Important Banks or SIBs continue to lead the Nigerian financial services sector despite their struggles with high non-performing loans (NPLs) and shriniking operating margins. The Central Bank of Nigeria (CBN) in September 2014, issued a framework for SIBs, which was […]

  • Qualitative education can curb violence, insecurity, says NDIC boss

    The Managing Director, Nigeria Deposit Insurance Corporation (NDIC), Umaru Ibrahim has advocated quality education as panacea to check the spate of violence and insecurity challenges currently being experienced in the country. The NDIC Boss made the remark in an address he delivered as the Keynote Speaker at the 15th Graduation Ceremony of Zaria Academy, Shika, […]

  • China offshore oil coy to invest $3bn in Nigeria

    The China National Offshore Oil Corporation (CNOOC) is to invest an additional three billion dollars in its existing stakes in offshore oil and gas operations in Nigeria. Mr Ndu Ughamadu, the Nigeria National Petroleum Corporation (NNPC) spokesman said this in a statement on Sunday in Abuja. Ughamadu said Mr Yuan Guangyu, the Chief Executive Officer […]

  • Ecobank risk assets deteriorate as Kie bows out

    By FELIX OLOYEDE The exit of Ecobank Nigeria’s erstwhile Managing Director, Charles Kie, has raised a groundswell of speculation in the financial community as sector analysts believe that his exit was abrupt, untimely and suspicious. Over a period of two years, Kie had succeeded in reversing the banks bedraggled balance sheet and profit and loss […]

  • Blood, blood everywhere: Herdsmen, rustlers on the rampage

    –  Violence, a well-articulated plot to grab land – Expert  By AYOOLA OLAOLUWA Nigeria is gradually descending into a Hobbesian state with the growing killings in the Middle Belt, in addition to the destruction of lives and properties in the North West and Boko Haram insurgency in the North East. Defenseless citizens are being killed like […]

  • 2018 budget in jeopardy

    . Delay alone has reduced performance by 13% – Experts By UCHE CHRIS In all likelihood the 2018 budget will end like the three previous budgets of the President Buhari administration: a failure. Having been passed seven months after its presentation and half year gone; and with all the controversies surrounding its passage by the […]

  • MTN to miss market listing target

    By OKEY ONYENWEAKU A weak domestic economy in Nigeria may force telecommunications giant MTN to shift its earlier proposed August 2018 date for a local listing on the Nigerian Stock Exchange (NSE). Analysts believe that the date shift will allow the parties to the Offer plan a more successful listing arrangement that would guaranty full […]

  • APC crises deepens: Amaechi battles for relevance, Modu-Sheriff is new strongman

    By OBINNA EZUGWU Key actors in the ruling All Progressives Congress (APC) managed to keep up appearance to allow for a smooth transition at the party’s recently held national convention. Except for the exchange of blows among Imo and Delta States delegates, the convention was largely a success. But beneath the facade of orderliness, tensions […]

  • INEC declares Fayemi governor-elect in Ekiti

    The Independent National Electoral Commission (INEC) has declared Kayode Fayemi of the All Progressive Congress (APC) winner of the Ekiti Governorship Election held on Saturday. INEC’s Chief Returning Officer for the election, Professor Idowu Olayinka declared the result on Sunday. According to the Returning Officer, Kayode got 197,459 votes to defeat the Deputy Governor of […]

  • President Muhammadu Buhari said on Wednesday that Nigeria will soon sign up to a $3 trillion African free-trade agreement. Nigeria is one of Africa’s two largest economies, the other being South Africa. Buhari’s government had refused to join a continental free-trade zone established in March, on the grounds that it wishes to defend its own […]

  • PDP meets Obasanjo for advice on how to beat Buhari in 2019 polls

    The National Working Committee (NWC) of the Peoples Democratic Party(PDP) will meet with former President Olusegun Obasanjo in Abeokuta on Saturday to seek advice on how to achieve victory in the 2019 polls and beat incumbent Muhammadu Buhari. The National Chairman of PDP, Uche Secondus, made this known in Abeokuta while addressing journalists after a […]

  • GTBank Launches Social Impact Challenge, Aims to Fund Community Development Projects Nationwide

    Following more than two decades of consistent investment in community development, Guaranty Trust Bank plc is taking its Corporate Social Responsibility (CSR) another step further by launching a Social Impact Challenge that will fund dozens of innovative ideas designed and executed by members of the general public. Tagged #SimpleChangeBigImpact, the Social Impact Challenge invites individuals […]