The cancer drugs in your bathroom cabinet

Researchers have had promising results treating tumours with everyday medicines. So why aren’t the big pharma companies investing in trials

Helen Hewitt lost her mother, her younger brother and her baby son to cancer. Having successfully overcome breast cancer herself, she is currently battling several tumours in her lungs, and – thanks to an inherited mutation in her DNA – is at high risk of developing other cancers as well. Yet Helen, 41, is pioneering an unfamiliar approach against this all too familiar foe. Alongside conventional chemotherapy, surgery, and radiotherapy, she is taking a cocktail of experimental yet well-known medicines. Some of them might even be in your bathroom cabinet.

One is the diabetes drug metformin, which besides making healthy cells more sensitive to the effects of the hormone insulin may also help to starve sugar-hungry cancer cells. The cholesterol-lowering statin and the antibiotic she’s been prescribed have the added benefit of dampening inflammation – a process cancer cells use to help them grow. Then there’s mebendazole, a common treatment for threadworm, which may also inhibit the growth of the blood vessels to her tumours.

Helen sought out these drugs after undergoing surgery to remove one tumour from her lung, only to discover that a different tumour had set up offshoots there as well. “It just made sense to try something that might weaken the tumours but wasn’t going to have a big impact on me in terms of side effects,” says Helen, an NHS podiatrist who lives inWolverhampton.
An early success story is thalidomide, whose resurrection as a cancer drug began in the 90s

Although the jury is still out on whether such drugs really make a difference, these aren’t the only medicine cabinet stalwarts undergoing a makeover. From aspirin to antacids, beta blockers to ibuprofen, all are being reinvestigated and utilised as potential anti-cancer drugs.

Unlike older therapies, which directly target and destroy dividing cancer cells, many of these repurposed drugs appear to work by targeting the healthy cells that cancers team up with to support their growth. Though widely accepted, this view of cancer as a mixture of deranged and healthy cells is still relatively new – which in part explains why the anti-cancer properties of drugs like aspirin may have been missed the first time around. “When many of these drugs were developed, we had a very simplistic view of cancer and all the focus was on finding ways of killing cancer cells,” says Pan Pantziarka, joint coordinator of the Repurposing Drugs in Oncology project, which aims to identify the most promising medicines for adaptation and get them into clinical trials. “But the whole system depends on developing a supporting blood supply, subverting the immune system, and producing certain growth factors. A lot of these repurposed drugs address these other things that cancer is dependent on to survive.”

An early success story is the controversial drug thalidomide. Originally developed as a sedative during the 1950s, it was later used to curb morning sickness during pregnancy, until it was found to increase the risk of severe birth defects and confined to the scrapheap. Thalidomide’s resurrection as a cancer drug began in the 90s, following the discovery that it inhibited the growth of new blood vessels. A series of case reports also indicated that it might suppress the immune system. Angus Dalgleish, a professor of oncology at St George’s hospital in Tooting, London, became interested in the drug after witnessing the dramatic turnaround of a patient with autoimmune disease who was treated with thalidomide. “I started doing some more reading and it struck me that here was a gem that had been thrown out with the rubbish,” he says. At around the same time, the results of a small trial of thalidomide in patients with the bone marrow cancer myeloma were published. The patients had failed to respond to standard therapy and were given thalidomide as a last resort; a quarter of them saw a reduction in their cancer as a result. But thalidomide had other side effects besides the awful deformities it generated in foetuses. So working with a startup company called Celgene, Dalgleish helped to develop several less toxic analogues, which were put into clinical trials. One of them was lenalidomide, today a blockbuster myeloma drug, which generates around $4bn in worldwide sales per year.

The controversial drug thalidomide, now repurposed an an anti-cancer drug. Photograph: AP

For now at least, thalidomide stands alone as a successfully repurposed anti-cancer drug. But it could soon be joined by aspirin, which has already taken on a new guise as a treatment for heart attacks and stroke. “There’s now some very interesting evidence suggesting that it might be a useful anti-cancer drug as well,” says Ruth Langley, a medical oncologist at the MRC Clinical Trials Unit in London. She is currently recruiting for a clinical trial of aspirin in around 11,000 patients who have already undergone the best available treatment for breast, colorectal, gastro-oesophageal or prostate cancer. “We are trying to see if, by giving aspirin, we can either delay the cancers coming back or even prevent them coming back altogether,” Langley says.
The idea comes from previous observations that people who take aspirin to prevent heart attacks seem to have lower rates of cancer than the general population, and if they do develop cancer it’s less likely to spread to other organs. Aspirin acts on particles in the blood called platelets and makes them less sticky. This reduces the likelihood of blood clots, which is why it’s used to treat cardiova scular disease. One theory is that platelets also surround cancer cells as they travel around the body, making them less visible to the immune system, but they do this less efficiently if someone is taking aspirin. Another theory is that platelets help cancer cells to anchor in new sites and set up new tumours.
Several trials are under way around the world, investigating the use of the beta-blocker propranolol (more commonly used to treat high blood pressure) in breast, ovarian and other cancers. These follow the discovery that propranolol can be used to treat non-cancerous birthmarks called haemangiomas – also known as strawberry marks – in children. “We said to ourselves, if it works in haemangioma, these drugs must inhibit the growth of blood vessels, so they could be useful to treat cancer too,” says Nicolas André, a paediatric oncologist at Hôpital de La Timone Enfants in Marseilles, France, who is about to start a trial of propranolol in angiosarcoma – a cancer of the lining of blood vessels.

And there are other candidates. The ReDo project has drawn up a list of the six most promising drugs based on their low toxicity, plausible mechanism of action and strong evidence of potential efficacy in humans. They are: the aforementioned anti-worm drug mebendazole; an antacid used to treat stomach ulcers called cimetidine; the angina drug nitroglycerin; a broad-spectrum anti-fungal called itraconazole; an antibiotic used to treat chest infections called clarithromycin; the anti-inflammatory painkiller diclofenac.
Yet despite the excitement surrounding these drugs, getting them into clinical trials is a long and arduous process. Unlike thalidomide, whose anti-cancer properties were spotted relatively early by someone with the clinical contacts to quickly move things forward, many of these drugs have been ignored, despite preliminary human trials with encouraging results.

Why is this? Surely pharma companies should be jumping up and down at the prospect of an effective, low toxicity cancer drug – particularly when the number of new cancer cases is projected to increase by 70% worldwide over the next two decades. In the UK alone, the number of people living with cancer is predicted to rise to 4 million by 2030, compared with 2.5 million currently. The trouble is that many of the existing drugs showing promise as anti-cancer agents have already lost their patents. “A drug company that invests money in supporting a clinical trial is not guaranteed to recoup that money if the trial is successful because some other manufacturer could come in and sell the same drug at a lower price,” says Pantziarka. “It’s a return-on-investment question.” Where clinical trials of these drugs have been done, they’ve generally been conducted by doctors and small groups of investigators. “They don’t have the time, experience or the money to take their positive results and change practice,” Pantziarka adds.

Ironically, their low cost is one reason repurposed drugs are such an attractive prospect. The average cost of new cancer drugs has increased from around £70 per month in the 1990s to more than £7,000 per month today; if this trajectory continues then we can expect the first £70,000 a month cancer drug by 2035, says Paul Cornes, an oncologist at the Bristol Oncology Centre. Part of the reason they’re so expensive is because it takes years of testing to ensure that any new treatment is safe and effective. But with repurposed drugs, many of these questions have already been answered. “We know they’re relatively safe, because they’re widely used,” says André. “Even so, we need sound, state-of-the-art clinical trials to confirm they work in cancer, and in order to get those we need funding.”

With investment from big pharma lacking, some groups are coming up with creative ways of getting these drugs into clinical trials. In November, doctors at St George’s hospital used crowdfunding to raise £50,000 to test the benefits of the anti-malarial drug artesunate on 140 patients with colorectal cancer. In an earlier pilot study of 20 patients, the cancer spread in six of the 11 given a placebo, compared with just one of the nine given artesunate. In this case, the drug appears to kill cancer cells directly, and it costs just 70p per day.

One of the huge advantages of using repurposed drugs is that you have a lot of toxicity information available already

Despite promising results like these, it could still be years before we know for sure if repurposed drugs work against cancer, and if so, how best to use them. But unfortunately, time is a luxury many cancer patients can’t afford. This has prompted some to take matters into their own hands.
One of them is Ben Williams, an experimental psychologist at the University of California in San Diego, who was diagnosed with an extremely aggressive brain cancer called a glioblastoma in 1995, aged 50. He immediately underwent surgery, and then radiotherapy, but his prospects looked bleak: the average life expectancy for patients with glioblastoma is just 15 months, with younger people more likely to survive. Williams expected to die within the year.

With little left to lose, he started searching for other drugs that might complement the chemotherapy he was about to start, using the biomedical literature database PubMed. This provided published studies of alternative glioblastoma treatments, many of which were repurposed drugs. When he identified a relevant-looking drug, he’d contact the researchers directly, asking for further information and advice about taking it. “Part of my strategy was that I needed to make the chemotherapy more effective, because it didn’t work most of the time,” says Williams. “If you’ve got a lethal diagnosis, then you’re going to have to take some risks to beat it.”
As a result, he started taking a cocktail of drugs more commonly prescribed for acne, insomnia and high blood pressure, as well as the breast cancer drug tamoxifen, which early studies had suggested might help to overcome resistance to chemotherapy. His oncologist was unimpressed. “He said, ‘you’re going to hurt yourself’, but I knew that I was less likely to hurt myself doing this than taking some of the stuff that he was offering,” says Williams, who travelled to Mexico to buy some of the drugs he wanted. “I was very much aware of the risks. But one of the huge advantages of using repurposed drugs is that you have a lot of toxicity information available already, because they have been used for such a long time.”

In Williams’s case, his treatment worked; against the odds, he remains cancer-free to this day. But even he admits he may have just got lucky and been one of the minority who responds well to chemotherapy: “I will never know whether any of these things I took made a big difference, and neither will anyone else.”

A scanning electron micrograph image of two prostate cancer cells in the final stage of cell division. Photograph: Steve Gschmeissner/Getty Images/Science Photo Library RM

However, there are good reasons why cancer patients should talk to their doctors, rather than self-medicating – even with something as seemingly innocuous as aspirin. “Firstly, we don’t know if it works, and secondly, even though aspirin is a very common drug, there are side effects,” says Langley. “There is a small risk of bleeding from your gut, or more seriously, even from your brain. We need to do proper studies and monitor safety very carefully.”

The same goes for other common medicines that may or may not have anti-cancer effects. “Even if they are effective, they are drugs that you probably need to take for long periods of time to see the effect – otherwise their effects would have been recognised before,” Langley adds.
Pantziarka, too, advises patients to work with their doctors rather than go it alone – and also certainly not to see repurposed drugs as an alternative to conventional treatments. 

“When we supply information to people, we encourage them to talk to their medical teams; we do not encourage them to go off and self-medicate.”

But not all doctors are open to new approaches, as Pantziarka knows only too well. He first became interested in the idea of drug repurposing when his teenage son, George, was diagnosed with terminal cancer in his jaw bone. Like Williams, he started researching published trials for his son’s condition on PubMed and then directly contacting the clinicians who had run them. The suggestions they came back with included a diabetes drug called pioglitazone, and another anti-inflammatory painkiller called celecoxib, in combination with continuous low doses of chemotherapy.

“My son’s doctor was not very positive,” Pantziarka says. “She said, ‘We don’t have any experience of these drugs’, and the argument that millions of people take pioglitazone for diabetes had no sway.” Eventually, she suggested a different combination of drugs, based on a protocol another doctor at her hospital had used previously. It was ineffective, and only made George feel worse. He died in April 2011, aged 17.

Doctors are understandably cautious about prescribing drugs for unlicensed uses; their peers may think them strange, and they may also find themselves in trouble if something goes wrong. But Dalgleish is one of those who is prepared to take these risks. He prescribes repurposed drugs for some of his cancer patients, and also liaises with their GPs and asks them to prescribe them, where appropriate. “I’ve had a lot of hassle for that,” he says. “There’s no room for freedom to do the best thing for your patients, just because someone hasn’t put up millions of pounds to do a big drugs trial.”

This is something that should at least partly be addressed with the Access to Medical Treatments Act which gained royal assent in March. It empowers the health secretary to create a database of innovative medical treatments, including off-label uses of existing drugs for cancer and other diseases. However, doctors still won’t be protected against medical negligence claims should something go wrong.

“It aims to raise awareness of the off-label use of repurposed drugs, to combat concerns about prescribing them and to ensure that they are used more consistently by clinicians,” says Nick Thomas-Symonds, Labour MP for Torfaen, who campaigned for it.

The government has also agreed to have information about the off-label use of drugs included in the British National Formulary – the pharmaceutical reference book used by doctors when prescribing medicines – and to develop an action plan to make it easier to gain new licences for drugs when they’re proven to be effective.

Helen Hewitt also found her NHS oncologist unwilling to prescribe the repurposed drugs she’d identified, so she found a private clinic in London where she could get them instead. She has been taking them since September, but last month she received disappointing news: the tumours in her lung have grown bigger. The next step is chemotherapy – something she’s been through before, but this time she’ll be taking her cocktail of non-cancer medications at the same time. “My hope, and the possibility, is that taking these drugs will weaken the tumour, so that when I do have chemotherapy there’s a better chance of it having an effect,” she says.

Her hope isn’t necessarily misplaced. If repurposed drugs do work, most experts agree they’re more likely to do so in combination with other drugs, rather than on their own. “I don’t believe in magic bullets; they are going to be part of combinations, and since they are fairly non-toxic and inexpensive you could use several agents more easily than when using standard drugs,” says André.

One of the problems with tumours is that they evolve, and most new cancer drugs are directed against a single molecular target. “Basic evolutionary biology tells us that cancer is a complex, adaptive system that evolves resistance to very closely targeted agents,” says Pantziarka. An advantage of these older, repurposed drugs is that they often hit multiple targets. Take diclofenac: it is often viewed as a relatively dirty drug because besides dampening pain and inflammation, it can irritate the stomach and slightly raise the risk of heart attacks and stroke. However, it may also inhibit the growth of blood vessels, modulate the immune system, and make the body more sensitive to the effects of radiotherapy and chemotherapy. It might be cheap and dirty, but that’s a lot of bang for a single tablet. Patients certainly shouldn’t see repurposed drugs as a panacea, but they’re at least worthy of hope.

By:  Linda Geddes

For more key trends go check out Daily Key Knowledge

These Top 5 Things That Could Kill Your iPhone

These are the top 5 things that could possibly kill your iPhone.

In my days of being on team iPhone I’ve definitely dealt with a few of these factors.

Share this message to raise awareness of ways to lengthen the life of iPhones to other users and potential users. You just never know who will view this message and be massively impacted by it.

Get $10,000 Per Child In College Tax Credits, Thanks To New Tax Deal (You Might Want To Check This Out) *Important*

The new tax deal has given the $2,500 a year American Opportunity Tax Credit (AOTC) permanent life instead of expiring at the end of 2017. The credit reduces your federal tax bill dollar-for-dollar by up to $2,500 per year for each eligible college student for whom you pay qualified tuition expenses. It can be claimed on behalf of an undergraduate for four years—that’s a $10,000 tax subsidy, over four years. And if you have more than one child in college at the same time, you can claim more than one credit.

This break had been set to expire at the end of 2017, after the fiscal cliff deal extended it for tax years 2013-2017. The new (December 2015) tax deal makes the credit permanently available, and that is good news for parents trying to pay for the high cost of college. The tax deal also made computers, iPads and tablets a qualified expense under 529 college savings plan rules.

The American Opportunity Tax Credit is worth more than the older college-related tax credits you might have heard of: the Hope Scholarship and Lifetime Learning Credits. It’s also more valuable than another tax break, the tuition and fees deduction. But understandably, having all of those credits creates a lot of confused taxpayers and leads some to miss out.

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How to Stream the NBA Finals On Any Device

In what’s sure to be a thrilling series, the Golden State Warriors are about to take on the Cleveland Cavaliers in the 2016 NBA Finals. Here’s how to stream every game on any device, as well as a few ways to catch the games if you don’t have a cable subscription.

Before we dive into how to watch, it might be helpful to know when to watch. Here’s the schedule for this year’s Finals, starting with the first game that’s airing tonight:

  • Game 1: Thursday, June 2, 9 p.m. ET / 6 p.m. PT
  • Game 2: Sunday, June 5, 8 p.m. ET / 5 p.m. PT
  • Game 3: Wednesday, June 8, 9 p.m. ET / 6 p.m. PT
  • Game 4: Friday, June 10, 9 p.m. ET / 6 p.m. PT
  • Game 5*: Monday, June 13, 9 p.m. ET / 6 p.m. PT
  • Game 6*: Thursday, June 16, 9 p.m. ET / 6 p.m. PT
  • Game 7*: Sunday, June 19, 8 p.m. ET / 5 p.m. PT

 

What You Can Stream With a Cable Subscription

If you have a cable subscription with major providers like AT&T, Charter, DirecTV, Dish Network, and Xfinity, you can watch the complete broadcast games at no additional cost via these web sites and apps:

You can also cast the game to your Google Chromecast or Apple TV.

Ways to Watch Without a Cable Subscription

If you don’t have a cable or satellite TV subscription, there are still a couple of ways to catch the games. For streaming, you either need to “borrow” a friend or family member’s cable login, or give Sling TV a try. Sling offers a seven day free trial period, and that’s long enough to let you catch the first three games for free. If you want to watch the rest of the finals, though, you’ll need to fork over $20 for a full month of service. All things considered, $20 to watch every NBA Finals game—plus all the other included channels—isn’t a bad deal, especially since you’ll be able to watch on iOS, Android, Roku, Xbox, Amazon, and other devices. And while there’s no app for the Apple TV yet, you can use your Sling credentials to access the games on the WatchESPN app.

You can also watch the games live on your TV if you have an HD capable over-the-air antenna. Just tune in to your local ABC affiliate. Last but not least, you can listen to each of the games for free via the ESPN Radio web site, or apps oniOS and Android

By: Patrick Allan

10 signs you will make it big one day

HINT: it’s neither about how smart, nor how hard you work.

We all have different definitions for “making it big”. For someone people, it’s about being able to stand on stage and deliver a performance to adoring fans. For others, it’s having readers cling onto every word that they read from your books. Yet for others, it could be having a popular YouTube channel where die hard fans tune in every week for your vlogs.

Regardless of how you define it, a common factor seems to be that you’re impacting people en masse, millions at a time. By impact, I refer to moving people in an emotional way.

You could be:

  • delighting,
  • inspiring,
  • firing up,
  • making them cry, or
  • making them take action.

A principle of marketing and human behavior is that people make decisions based on emotion and justify with logic. We want to be perceived as being rational and logical, but every one of us — even people who swear they make decisions based only on science — will ultimately make them based on how we feel.

If you make it big, you’re essentially affecting thousands or maybe millions of people in such a way that you can act in a certain way. It sounds like mind control, but celebrities and people constantly in the media do it all the time.

You might want to change the world. You might feel like impacting millions is the best way to go about it. That’s why I’ve compiled this list of characteristics I’ve observed of people who have done exactly that.

Here are 10 signs that you will make it big some day:

1. You think in terms of years, not months.

Someone doesn’t go from obscurity to mega star over night. Bar viral sensations (that always fizzle out if the spark isn’t kept alight), building up a reputation takes years.

Gary Vaynerchuk has said before that if you’re not willing to put in two to three years into what you’re trying to do, your idea won’t have the time to gain traction.

We as a whole are also becoming more and more distrusting. The cacophony of ads is getting louder and louder. We’re having to tune out nearly all the time, making it harder for anyone to be heard.

This is a blessing in disguise. You see…

We are listening for the quiet people whose statements make the noise.

A well-thought out message that cuts through the clutter is truly rare and hard to find. You need to spend the time to make it heard. And when it is, people will talk about it.

2. You ARE in it for the money.

Yep, you read that right. You’re all about the dollar signs. You’re probably expecting me to say “not”, but there’s a valid reason why I think money matters if you’re trying to make it big.

No matter which way you look at it, money makes the world go round. We might hope for a utopia, but the game is played by certain rules. While certain rules can be broken, the money rule cannot.

Now, this doesn’t mean that I think we should all go in with the intent to charge for everything we do. Philanthropy still has an important role to play. But even with that, you need money to make an impact.

To make it big, you need to impact millions of people. To do this, you have to create something that adds value to their life. To value it, they have to pay for it with money.

The size of the problem you solve determines how much money you can make. It also determines the level of impact you can have on people. So don’t shy away from making money. You will be able to help more people that way.

3. You genuinely care about the people you wish to affect.

This sign is a given. Even if you are impacting people millions at a time, you see each person as an individual. You have a crystal clear idea of who the ideal customer, the typical follower or average fan is, you can name their fears and hopes and you know what they’re expecting out of you.

In marketing, this is called an avatar. It should be used by anyone looking to make an impact to many people.

The thing you’re creating is useless if you don’t know who it’s for.

People will not support you just because you make something cool. They will support you because you care about what they want and are trying to solve their problem in a way only you can.

Creators and entrepreneurs have to accept responsibility for who they are. The moment they decide they want to make it big, they have to realize that people put them on a pedestal.

They look up to them and admire them because they aspire to be like them, all because they care for them. It’s not easy, but it’s the cost to impact people at scale.

4. You focus on the $10,000 per hour jobs.

The work we do can be classified into different categories. At a day job, we do work that, on average, ranges from $10 — $30 per hour. However, in reality we know that our level of output isn’t worth the same amount every hour.

Someone might come in to work not completely awake yet. They have their morning coffee then — BOOM! — their productivity shoots up. Their hourly rate is suddenly worth closer to $50, maybe $100 an hour. This would fluctuate on a daily basis.

Then you have different classes of jobs. Surgeons, lawyers and senior management are worth $100’s, maybe even $1,000’s an hour. That’s because the problem they solve is expensive or involves something extremely valuable.

When you make it big and are impacting a lot of people, you’re multiplying your impact many times. You’re also solving a big problem, be it entertainment, making sales or something else. That’s why your work can be worth $10,000/hour. It might even be worth six to seven figures an hour!

Someone who makes it big as people they delegate their $10 to $100/hour jobs to. These are jobs like admin, reception, management, responding to emails and putting out daily fires.

Someone who’s made it big focuses on the work that has made them big. Someone who does everything will never make it big.

Some people are scared that someone else will not be able to do a certain task as good as they can. Guess what? They’re right. They won’t. But that’s the cost of becoming an influencer.

5. You look for “no’s”, not “yes’s”.

Jon Westenberg wrote a piece recently about loving the word “no”. Society operates harmoniously when everyone is in agreement. Conflict, in general, is seen as a bad thing.

It depends on the scale. I would concur that agreements do strengthen the fabric of society. Truces are agreements between warring nations to stop fighting. Business agreements can help solve more problems that companies couldn’t solve on their own.

However, the agreements would have taken several “no’s” to get to.

The truth is…

The negotiation hasn’t started until you hear “no”.

Some people cannot commit to either yes or no. They aren’t the people who can help you. Nor are the people who say yes to everything. They are usually hiding something.

Someone who has something that you want and wants something from you will tell you “no”. They want to reach an agreement and want to reach a middle ground with you on which you both get what you want.

So always look for the “no”. That’s when you know you are finally moving up.

6. You’re improving every single week

James Altucher wrote a piece earlier in the year, suggesting that people improve 1% a day. I responded to it with my most popular piece on Medium so far, 52 ways to make life 68% more rewarding.

Why 68%? I did the maths and a 1% improvement a week compounds to a 68% improvement in a year, which isn’t too shabby at all. If you are able to consistently grow by 1% a day in your chosen field, all the more power to you. I couldn’t do it, since I would burn out.

People who make it big are constantly growing. The term is a bit of a misnomer; you don’t ever “make it”; you just keep growing. You do things that scare you, you do things that give your life meaning and you choose your own suffering.

As I mentioned in the first point, no one goes from zero to hero overnight. Even if you did, you don’t want to become a player in that way. It wouldn’t feel right. You cheated the system and you cheated yourself.

It’s the reason why I started the 100 Naked Words publication, where I along with select writers write 100 words a day. It’s a great habit, you grow and your writing gets exponentially better. Plus, we’re impacting readers who draw inspiration from our daily words.

7. Your five closest friends are influencers.

The people you surround yourself with are what you’re composed of. Obviously you’re all different people, but their habits, rituals and hobbies are shared. Birds of a feather flock together, after all.

Unless you’re going out of your way to find people to befriend who are in a higher league than your own, you won’t become a part of that league.

No one makes it big on their own.

This is the hardest point to achieve. Our friends might have been with us from day one, but if what you seek is growth, you might have to place less emphasis on that friendship.

This isn’t to say that you can’t stay friends with them. If you both have a dream to make it big, then you support one another. This is the ideal path. However, people are all different and it would be selfish to pull an unwilling friend into your dream if they don’t share your vision.

Getting to know people who have done the hard yards is the only real shortcut there is to making it big. They are already an influencer, so by promoting you to their followers can bestow that clout to you.

Of course, you have to be a genuine friend and be doing something that aligns with their own goals. That’s why it’s important to be conscious with who you align yourself with. So many people just fall into the wrong crowds and then wonder why their life ends up a certain way.

8. People are discouraging you all the time.

These people are the ones who care about the most: friends and family. They don’t want to see you get hurt, waste time or money or end up disappointed.

They mean well, but take what they say with a grain of salt. Most, if not all, of them haven’t done what you’re trying to do before. They’re looking at you from their safe, warm shells while you’re out in the firing line.

They seek the familiar, while something pulls you outside to stare into the abyss of the unknown. It doesn’t scare you one bit. In fact, you feel like jumping in.

If people are trying to stop you from doing what you’re trying to do, that’s a great sign. It means that you’re on the right path of making it big.

People don’t make it big doing normal things. Normal things have normal limits. Unusual things that have no perceivable ceiling are exciting. They’re also frightening to certain people who like that security.

This can only take you so far, though. Eventually, you will have to find a mentor, someone who’s gone down your path, heard all the negativity and still come out on top. But if you don’t have someone like that, discouragement from normal people is a good place to get your bearings.

9. You focus on the problem, not on the product.

If you want to be successful in anything, this is the order of “P’s” you should always remember:

Problem > People > Product

Whatever you’re trying to do, if you’re focused on the problem you’re trying to solve, making it big will become inevitable.

This advice is common sense, but in this day and age, even with the level of insight you can gain into what people think and feel, people still fall in love with their ideas and completely forget about the people whose problems they’re trying to fix.

You don’t have to have all the answers. In fact, having the humility to ask the people who support you what they want from you can actually enamor them even more to you.

No one has the guts to be authentic and human. That’s what inevitably leads to their downfall. Have the courage to ask and understand the real problems and your people will always welcome you.

10. Settling scares you.

I don’t know about you, but imagining myself in 10 years being in the same place as I am now terrifies me. Being a nobody when I could have been a somebody terrifies me. The fear comes from the “could have been” part.

If you’re anything like me, you’re someone who’s been told several times that you have potential. It’s the extent that you believe that statement that defines who you want to become.

Let’s face it:

We all have potential. We’re unique but we’re not special, or different. We all can be someone, but how much we want to become that person is what shapes your actions from today.

Believe it or not, some people are content with just dreaming about what their life could be like. They get a rush from their imagination, then they go back to playing Candy Crush and distracting themselves from the mediocrity of their lives. Sounds crazy, right?

The last thing I would want is to wake up, realize I’m 43, have two kids who don’t think their dad is the best man in the world anymore and a wife who accepted that she chose the wrong partner.

How many of these things can you tick off? Are there any that I’ve left out? Or are there any that you don’t think should be on the list? Let me know in the comments.

By: Johnson Kee