Researchers at MUSC Hollings Cancer Center believe that some drugs already approved by the U.S. Food and Drug Administration or currently in clinical trials could be repurposed for certain breast cancer patients whose cancer has become resistant to standard therapies.
Credit: MUSC Hollings Cancer Center
Researchers at MUSC Hollings Cancer Center believe that some drugs already approved by the U.S. Food and Drug Administration or currently in clinical trials could be repurposed for certain breast cancer patients whose cancer has become resistant to standard therapies.
Ozgur Sahin, Ph.D., a professor and SmartState Endowed Chair in the Department of Biochemistry and Molecular Biology, led the research, which was published Nov. 2 in Nature Communications.
The research, funded by an American Cancer Society Research Scholar Grant, started as an investigation into cancer resistance to the drug tamoxifen but expanded as the research questions led down new avenues, encompassing other hormone therapies and CDK4/6 inhibitors. CDK4/6 inhibitors are targeted therapies that stop cancer cells from multiplying.
The result is a new explanation of why certain widely used therapies work – and by better understanding how these common therapies are actually functioning, researchers can formulate new therapies to respond when they stop working.
Christina Annunziata, M.D., Ph.D., senior vice president for extramural discovery science at the American Cancer Society, praised the work.
“The American Cancer Society is proud to support Dr. Sahin’s research into overcoming resistance to therapy in ER-positive breast cancer. This study underscores his novel approach to understanding molecular mechanisms of resistance underlying metastatic recurrence; as such, his research helps advance our mission to ensure that everyone has an opportunity to prevent, detect, treat and survive cancer,” she said.
“The most important thing here is that there are inhibitors for all those three which are either FDA-approved for different cancers, or they are in clinical trials for other non-cancer diseases.”
Ozgur Sahin, Ph.D.
Sahin focused on estrogen receptor positive, or ER-positive, breast cancer. ER-positive breast cancer, which accounts for about 75% of all breast cancer cases, uses estrogen to grow. Women with ER-positive breast cancer may use hormone therapy after surgery to prevent the cancer from returning or, if the cancer has already spread, they may use it to slow or stop its spread. CDK4/6 inhibitors may be used at the same time as or after hormone therapy, depending on the specific diagnosis.
However, some patients may find that their cancer develops resistance to hormone therapy and CDK4/6 inhibitors.
“What we wanted to do in this study was to identify the initial question of how these therapies work and why they don’t work when patients develop resistance. And the third thing is – how we can make them work again?” Sahin said.
Cancer drugs are broadly divided into two categories based on how they act. Cytotoxic drugs kill cancer cells and cytostatic drugs slow or prevent cancer growth.
Hormone therapy has been categorized as cytostatic because it blocks estrogen receptors, but Sahin said his team found a new mechanism by which hormone therapy, also called endocrine therapy, is acting.
“What we show here is they are actually inducing DNA damage like chemotherapy agents,” he said. “This is so surprising and intriguing because we’ve found that these endocrine therapies and CDK4/6 inhibitors induce DNA damage with inhibition of homologous recombination, leading to toxic PARP trapping and cell death.” Recombination is a process by which pieces of DNA are broken and recombined to produce new combinations. PARP is a key protein involved in DNA repair.
“And since PARP is trapped on the chromatin, the transcription [the process of copying a gene’s instructions onto messenger RNA in order to build proteins] cannot happen. This is beyond the known blockage of estrogen receptor-dependent transcription by endocrine therapies,” he explained.
“We show that this is happening because when we give the standard-of-care therapies, they induce cyclic AMP,” added Ozge Saatci, a senior graduate student in the Sahin Lab and the first author of the paper. “These are second messengers in the cells. They are small molecules, and they have a lot of functions, but since these standards-of-care therapies lead to accumulation of cyclic AMP, so they generate reactive oxygen species, which leads to DNA damage.”
Sahin added that when cancer cells become resistant to hormone therapy, what is actually happening is that the cancer is becoming less dependent on estrogen to grow. Instead, it turns to other molecules like epidermal growth factor, or EGF.
Sahin’s team showed that targeting epidermal growth factor receptors (EGFR) or phosphodiesterase or using PARP inhibitors would overcome the cancer’s resistance to standard therapies.
“The most important thing here is that there are inhibitors for all those three which are either FDA-approved for different cancers, or they are in clinical trials for other non-cancer diseases,” Sahin said.
For example, a phosphodiesterase 4D inhibitor is in clinical trials for Fragile X Syndrome, a genetic disorder that causes developmental delays and intellectual disabilities, particularly in boys. Another clinical trial is testing PARP inhibitors in combination with endocrine and CDK 4/6 inhibitors. However, Sahin noted that the trial targets patients with BRCA mutations, and his team’s research indicates that the PARP inhibitors could also work for patients without BRCA mutations.
About MUSC Hollings Cancer Center
MUSC Hollings Cancer Center is South Carolina’s only National Cancer Institute-designated cancer center with the largest academic-based cancer research program in the state. The cancer center comprises more than 130 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and sponsors more than 200 clinical trials across the state. Dedicated to preventing and reducing the cancer burden statewide, the Hollings Office of Community Outreach and Engagement works with community organizations to bring cancer education and prevention information to affected populations. Hollings offers state-of-the-art cancer screening, diagnostic capabilities, therapies and surgical techniques within its multidisciplinary clinics. Hollings specialists include surgeons, medical oncologists, radiation oncologists, radiologists, pathologists, psychologists and other clinical providers equipped to provide the full range of cancer care. For more information, visit hollingscancercenter.musc.edu.
Journal
Nature Communications
DOI
10.1038/s41467-023-42736-y
Article Title
Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer
Article Publication Date
2-Nov-2023
COI Statement
O. Sahin is the co-founder and manager of OncoCube Therapeutics LLC, developing TACC3 inhibitors, and the founder and president of LoxiGen, Inc, developing lysyl oxidase inhibitors. The other authors declare no potential conflicts of interest.
That’s right, the asset class everybody hates and thinks will collapse the banking system, the government, and everything except companies that make AI-related semiconductor chips.
The media hates it.
The clickbait hunters love the stuff because it is so easy to craft doom-and-gloom marketing measures around empty offices and defaulted loans.
But the truth is, now is the perfect time to start buying. Here’s why…
Don’t get me wrong.
We have not seen the end of the ugly headlines by any stretch of the imagination.
Downtown office towers are still going to have some problems.
Some of the overleveraged ones will still be working their way through the stages of foreclosure.
Most are still in disbelief, with bargaining, plotting, pleading, begging, and throwing the keys at the lender’s head in disgust still to come.
We could have months of ugly headlines from the office sector.
Most troubled properties will be big city center city towers in gateway markets.
Class B and C apartments may have some problems as well.
Is it really the bottom? The absolute bottom in real estate?
I doubt it. I have never picked an absolute top or bottom; I suspect that will not change anytime soon.
We could see lower prices before the markets reverse and go higher.
It may be months, or even a year or more, before the markets start to get excited about commercial real estate again.
I prefer it that way.
The longer it takes, the more time I have to find and buy quality real estate-related opportunities.
I do not know when the absolute bottom in real estate will be.
Here is what I do know:
Big and tech companies are starting to push for workers to return.
The vast majority of people will not quit a good-paying job to avoid commuting.
Class A offices are filling up as tenants use the current market weakness to upgrade.
The same flight to quality is happening in cities large and small when it comes to apartments and rental housing.
The migration to states with warm weather and lower taxes will continue.
People with good jobs and full bank accounts will still go shopping.
The very best malls, both indoor and outdoor, will continue to thrive
We will still go to pharmacies, grocery stores, and other necessary retail locations.
Our national fascination and attachment to “stuff” will keep the self-storage facilities full.
People who have discovered and fully embraced the lazy delights of shopping from home will keep warehouses in high demand.
The lessons of the pandemic’s early days will continue to drive demand for new local warehouse space for many retailers.
Some commercial real estate loans will default. Most will not.
So far, I am finding opportunities for my members and myself in high-quality REITs, real estate, corporate debt, preferred stocks, closed-end funds, homebuilders, and real estate services companies.
I strongly prefer opportunities that throw off a lot of cash.
Cash coming in the door makes it much easier to wait for prices to settle down and begin to head higher again.
While only a few people are moving to buy real estate right now, I am not entirely alone.
Jonathan Gray, the President of Blackstone, recently said, “The perception is so negative, and yet the value decline has occurred, so when you get into this bottoming period, that’s when you want to move.”
He added “As investors, sometimes, one of the risks is that you miss it by being overly cautious, and I think now is probably a good time before rates come down.”
Blackstone is one of the world’s largest owners of commercial real estate properties. I think they might know what they are talking about regarding the opportunity I see developing in commercial properties.
I will hold most of the assets and companies I am buying today until everyone wants to own real estate, and real estate speculation promotions have replaced all the options trading ads.
There are a few world-class assets that I suspect I will hold forever.
Many debt-related investments will be sold at a premium when real estate is upgraded, or the Fed cuts rates.
We could see a double whammy that delivers a two-for-one pop in the price of real estate-related debt over the next year or two.
I don’t know when the exact bottom will occur in real estate.
However, I am absolutely certain that in a few years, my readers and I will be very happy with the high-quality, high-grade real estate investments we are making today.
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(Featuring: The Three Big Lies of “Climate Action”)
Everybody talks a good game when asked about environmental concerns. But they underestimate what real “climate action” will cost them, personally, and they’re prone to balking when they figure it out.
In 2018, The Energy Policy Institute at the University of Chicago conducted a survey of 1,202 people asking them if they thought climate change was an issue, and if so, how much were they willing to contribute, out of their own pockets, towards “fixing it”:
71% of the respondents said that climate change was a reality, and most of those thought human activity was largely responsible for it.
57% said they’d be willing to spend $1/month, or $12 annually.
23% were willing to go big: $40 a month, in order to “fix” climate change.
A more recent study of ten European countries in 2021 found that most people feel as though they are already doing their part to live a climate conscious lifestyle – and further – they are individually doing more than those in the media, or their governments (hold that thought).
In other words, while most respondents believed that there was an impending climate crisis, they also believe they had already made all the personal lifestyle adjustments they’ll need to make in order to address it.
These attitudes are pretty typical of a populace who has already undergone massive conditioning by the media and academia around climate alarmism, but who otherwise live largely insular, bubble-wrapped lifestyles and think food comes from Uber Eats.
They have no idea that that climate targets, like “netzero” or Agenda 2030 will cost more them more than a few hundred bucks a year, per person, to “fix”.
Even with carbon taxes becoming more prevalent – citizens think the extent of the impact on their lives are the economic pressures of them inexorably rising (here in Canada, the carbon tax went up 23% on April 1st, the same day all federal Members of Parliament got a pay raise).
That’s bad enough – but people are still completely unprepared for what has already been decided from on high for their personal destinies:
Climate Action requires a complete re-ordering of society and civilization itself.
“De-carbonization” requires “#degrowth”, a euphemistic hashtag that really means forced austerity on all of humanity – save for those apparatchiks imposing it on the rest of us.
The Big Lie of climate alarmism is threefold:
That the climate goals of netzero and decarbonization can boost the economy and increase prosperity for all
That achieving said goals will afford us control over the climate and alter the planetary physics of the earth itself
That this is all “settled science”
Let’s look at each of these in order:
Big Lie #1: Pursuing Netzero will boost prosperity
Many politicians like to gaslight us that there is a way achieve netzero targets in an economically beneficial manner. A good example, again here in Canada – is the carbon tax.
Everybody pays the carbon tax – on gas, on flights, on heating their homes, etc. Most households get a “carbon tax rebate” – which is invariably, for less money than they have paid in carbon taxes. This is borne out in countless analyses on this, including the government’s own Parliamentary Budget Office report, which found that:
“most households will experience a net loss of income from the federal carbon tax, even after rebates.
Specifically, in fiscal year 2024-25, 60 per cent of households in Alberta, Ontario, Saskatchewan, Newfoundland and Labrador, Nova Scotia, Prince Edward Island and Manitoba will pay more in carbon taxes than what they receive in rebates, after accounting for both direct and indirect costs of the carbon tax. By 2030, 80 per cent of households in Alberta, Ontario, Manitoba, Nova Scotia and P.E.I. will be worse off, as will 60 per cent of households in Saskatchewan and Newfoundland and Labrador.
Indeed, according to the PBO estimates, the carbon tax will cost the average Canadian household between $377 and $911 in 2024-25—even after rebates, with Albertans being the most affected. As the carbon tax escalates annually, the financial burden will intensify. By 2030, the carbon tax’s average net cost for Canadian households will rise to $1,490 in Manitoba, $1,723 in Saskatchewan, $1,820 in Ontario and $2,773 in Alberta.”
— Via Fraser Institute
Yet the Trudeau government frames the rebate as “free money” for Canadians, and demonizes anybody who wants to “Axe The Tax” as though they are trying to take money away from taxpayers.
The Libs are going keep doubling-down on the nonsensical claim that #AxeTheTax would actually take money away from Canadians.
— Mark Jeftovic, The ₿itcoin Capitalist (@StuntPope) April 6, 2024
If decarbonization was economically viable, then it would be happening on its own, without governments and the corporate media relentlessly brainwashing us to do it.
For example, we would probably have mini-nuclear reactors all over the place by now if private industry was given some latitude to implement it.
Big Lie #2: Achieving Netzero will enable us to control the planet’s climate
There has perhaps never been a more grandiose and categorically impossible vision for humanity than the one where technocrats and experts can massage the trajectory of global climate through the judicious employment of carbon taxes, personal carbon footprint quotas and forced collectivism.
On the planetary level – it makes no difference if a country like Canada decarbonized 100% – compared to the emissions of China alone. Right now they’re lighting up two new coal fired plants every week. Wake me up when they decarbonize.
Not to mention numerous other countries who have no intention of foregoing their shot at economic prosperity at the behest of already an affluent (not to mention overly sanctimonious), West…
“Let me stop you right there…”
Caribbean nation Guyana is booming after discovering oil. BBC’s Stephen Sackur puts it to President @presidentaligy; lobbyists say oil is bad for the climate.
The discrepancies in values and aims between nation states already makes the 100% conformity that climate action requires a non-starter.
That doesn’t even account for things we absolutely can’t control like the solar system itself.
The best and brightest minds can’t even get interest rates right, nor “manage the economy” and that’s near 100% human driven. What are we supposed to do about the elephant in the room in terms of the single most relevant driver of climate cycles here on the planet: the sun?
Our sun outputs an estimated 6 billion times more energy per second than all of humanity generates and consumes in an entire year. It is the likeliest candidate for what drives long term heating and cooling cycles, not only here on earth – but throughout the entire solar system.
Granted – that energy radiates in all directions – if you only count all the energy that actually hits earth, that number drops: to 100 million times annual energy usage, per second.
No amount of carbon taxes or collectivism is going to overpower that.
Big Lie #3: The Science Is Settled™
Decades of propaganda and operant conditioning has browbeat the public into believing, or at least not arguing, that “the science is settled” when it comes to climate. One of the most well worn tropes around this is “97% of climate scientists agree” that “humans are causing global warming”.
In 2013, Australian researcher John Cook analyzed 11,944 peer-reviewed papers on climate change, from which the famous, mystical 97% figure emerged. It later came out (via UN lead author Richard Tol), that of those papers, 66.4% expressed “no opinion at all” on human-caused global warming. Those were eliminated.
The minority of papers that were left, and did express an opinion, were mostly on the same page, and Cook took his 97% from that.
What is actually true, however, from the study’s own numbers, is this:
11,944 papers were analyzed
7,930 of them expressed no opinion on AGW (66.4%)
97% of the remaining 4,013 papers did
So it turns out that 97% of climate scientists do not agree that humans are causing global warming. It was more like 32.5% (97% of 33.6% of 11,944).
Doesn’t have the same punch, does it?
Of course, since then, 97% became Holy Canon. So much so that any climate scientists who knew what side of the bread the butter was on, got the message loud and clear: your academic career depends on aligning with the consensus.
So called “climate deniers” are continually deplatformed and countervailing data suppressed. This may be changing, again owing to widespread disenfranchisement with how the “experts” managed the pandemic, the public seems to be more questioning.
The recent Climate The Movie: The Cold Truth has gone viral – and in it we see how the machinations of Big Climate may be driven more by junk science and hidden agendas than an altruistic desire to protect the environment.
So it’s no surprise then, that the climate alarmists are turning out in full force to have it suppressed:
I'm thinking we can get 10,000 people to report "Climate: the Movie" on YouTube as having harmful and misleading content.
After the botched policy responses to Covid, when it comes to climate, the public increasingly isn’t buying it. We’ll see this in action when the Canada’s Liberals, who have clearly gone “all in” on climate, lose the next election. I’ve been predicting a 1993-style blowout (when Bryan Mulroney’s deeply loathed Conservatives lost all but three seats, including their party status).
However, the public seemingly possesses but a single lever to resist all this: the ability to vote out politicians hellbent on impoverishing them.
But if the rabble continues in its propensity to vote the “wrong way”, how much longer will they be permitted to do so?
As we’ll see below – this lever will have to be rescinded, because otherwise the world will end.
Which is why the only forward course of action is political, economic and cultural tyranny.
If the plebs won’t voluntarily accept climate action – it will have to be forced on them.
The unpleasant truth is – if policy makers are serious about achieving netzero, it will require a massive policy of degrowth that will impoverish the masses and demolish the economy – none of which is conducive to being re-elected.
Which means: if world governments are serious about climate action, they will have to impose a totalitarian dictatorship to achieve it.
This has already been understood and internalized by the mainstream corporate media – after experiencing the destruction of their monopoly on “news” at the hands of the internet – have aggressively pivoted into a new business model: that of being propagandists for eco-Marxism.
Academia is right there alongside, putting out research papers to enshrine climate collectivism into the public discourse, and freeze out any dissenters.
In “Political Legitimacy, Authoritarianism, and Climate Change”, Ross Mittiga, a professor of Political Theory at the Catholic University of Chile (and Democratic Socialist) argues that political aspirants should not even be permitted to seek office unless they pass a “climate litmus test”;
“Governments might also justifiably limit certain democratic institutions and processes to the extent these bear on the promulgation or implementation of environmental policy. This could involve imposing a climate litmus-test on those who seek public office, disqualifying anyone who has significant (relational or financial) ties to climate-harming industries or a history of climate denialism.”
“More strongly, governments may establish institutions capable of overturning previous democratic decisions (expressed, for example, in popu- lar referenda or plebiscites) against the implementation of carbon taxes or other necessary climate policies.”
”what do truly low-carbon lifestyles look like – and can they really be achieved by personal choice alone?“
Future Labs – also out of the UK – put out a paper on the future of travel last year, that predicted mandatory “carbon passports” that would limit one’s travel based on their C02 footprint:
A personal carbon emissions limit will become the new normal…
These allowances will manifest as passports that force people to ration their carbon in line with the global carbon budget…
By 2040, we can expect to see limitations imposed on the amount of travel that is permitted each year.
Experts suggest that individuals should currently limit their carbon emissions to 2.3 tonnes each year
This last line is important – because it puts a number to how far down the rabble is expected to ratchet down their living standards: it’s about onequarter of what the typical G20 citizen emits today – by 2040, and “experts suggest” that gets cut again by half by 2050.
In the carbon passports article I laid out a table showing by how much individuals in each country would have to ratchet down their output to meet the personal carbon allowances, set by unelected and unaccountable experts:
Both politicians and their appointed apparatchiks are being more open about their ideologies and decidedly collectivist aims:
In 2023 a federal report published by Health Canada openly advocated for the dismantling of capitalism itself, equating it with white supremacy and colonialism – attributing them all as core drivers of the climate crisis. Another term for “capitalism” is “free markets”.
The report also advocated for collectivism and decried individualism as “one of the core values of society that has to change”:
“The hopes expressed by participants encompassed such a vision of collectivism”
“there are 3 core values in western society, and for that matter, in global society, that have to change. One core value is about growth and materialism. The second core value is liberty and individualism, which has to be rethought because the kind of individualism that is preached by neoliberals is part of the problem. It advances the individual over the collective… it leads to a huge number of problems, and it undermines the collective process”
“If we don’t address capitalism, if we don’t address colonialism, racism, the patriarchy, et cetera, we’re going to tread water for a long time until we eventually drown …”
As I remarked at the time: this was not a think piece or a screed from Vox or Jacobin Magazine – it was an official Canadian government report issued in the name of “His Majesty the King in Right of Canada, as represented by the Minister of Health, 2023”.
Canadian politicians across all parties have been coalescing around climate authoritarianism for decades. In 2007, Canada’s Laurentian Elite met in Merrickville, Ontario to discuss how best to advance the climate agenda – and was later analyzed via a series of interviews with the participants who comprised a who’s who of Canadian dynastic wealth, corporate power, politics – and media.
They transcended party boundaries: Former Prime Minister Joe Clark, Justin Trudeau bagman Stephen Bronfman, Patrick Daniel (Enbridge), Stéphane Dion, former Quebec premiere Pierre Marc Johnson, WE Charity co-founder Mark Kielburger, the list goes on.
From the “strictly confidential” briefings which are openly linked from this UCLA professor’s web page we learn how Canada’s elite ruminated about the lack of action on climate change, and how untenable the required societal mobilization would be in a democracy:
“It is impossible to have real conservation in a democracy! What is needed is a benevolent dictator—globally, and in Canada.”
During the proceedings…
“…many speakers express a longing for an authoritative decision process that somehow takes the issue out of the political arena. Some express this as the need for a “benign dictator;”
This move toward climate authoritarianism is spreading throughout the neoLiberal world order – most recently in Germany a “Climate Justice” report by the German Ethics Council concluded that “restricting freedoms may be necessary to fight climate change”.
“Responsibility presupposes freedom, and freedom includes responsibility. This principle also applies for climate change; it is crucial for our free and democratic society and safeguarded and guaranteed by law. Social coexistence requires mutual restrictions of freedom, in order to provide equitable freedom for all.“
“The inner and rationally guided realisation of the necessity for action leads to self-commitment as an expression of one’s individual freedom. This may imply that people question their former lifestyle or adapt their behaviour, for example by voluntarily abandoning certain vacation, consumption or mobility practices.”
And the Orwell Award goes to:
“On grounds of justice, it can be morally required to contribute to measures to tackle climate change. If one’s own exercise of freedom interferes in an unjust manner with the freedom and welfare of others or of future generations, for example through consumption that is harmful to the climate, the authorities may intervene with restrictions of freedom.
As long as there is no regulatory obligation, it is left up to the individual to accept a moral obligation to co-operate.”
We could probably even riff out one of those Martin Niemöller “First They Came For…” poetic reboots:
“First they came for the Bitcoin miners (but I didn’t care because I was a no-coiner)…” (or one of those PoS retards).
“Then they came for…” yada yada yada – guess how it ends?
“Then they came for me, because of my heated bathroom floors”
There’s only one other problem with all this…
#Degrowth For Thee, But Not For Me
It’s not bad enough that your consumption choices are being decided for you by unelected technocrats informed by garbage computer models predicting an unfalsifiable eco-Eschaton.
What’s worse is that while you’re personal standard of living is going to be attenuated, metered, capped and regulated (this is what the coming CBDCs are all about) – the apparatchiks, functionaries and career politicians who force this on you will not ratchet back their own consumption patterns, not at all.
When I reported on COP26’s takeaways (basically, they’re coming after your meat consumption), what stood out the most was the hypocrisy of a strategic objective emerging from an elite conclave that was arrived at almost exclusively by private jet, and whose culinary menu contained some of the most carbon heavy delicacies available. High grade Scottish haggis and venison were served, soy protein and bugs were not.
This is the rule, not the exception. Canada’s environment minister, who doesn’t mince words that “fighting climate change is about limiting your energy usage”:
Canadian Environment Minister Steven Guilbeault rather blithely answering a reporter who asked "will the government limit natural gas usage in the winter?"
— Mark Jeftovic, The ₿itcoin Capitalist (@StuntPope) November 25, 2023
But has no qualms around spending millions of dollars flying his entourage out to COP28 and staying in a $2,000/night luxury hotel suite.
Everybody else needs to ditch their cars, eat bugs and decolonialize extractive capitalism so that “proud socialists” like this fuck here can fly out to COP28 on a private jet and live large… https://t.co/a7fYsH52sy
— Mark Jeftovic, The ₿itcoin Capitalist (@StuntPope) March 20, 2024
Never forget this: whenever you hear politicians, “experts”, policy wonks and especially celebrities talking about the need to dial back consumption, energy usage, travel, meat consumption and even owning petsin order to “Save The World” they aren’t talking about their own lifestyles. They’re talking about yours.
The Public Has Had Enough
Earlier I mentioned how there’s basically one lever the public can use to skate eco-authoritarianism into the boards, and that’s the electoral process – which is why we wonder out loud how long those will be allowed to continue.
Here’s Klaus Schwab navel gazing with Sergei Brin about how Big Tech and algorithms will make elections unnecessary, “because the algos will already know who is going to win” (he poses this hypothetical about a minute after he says “in ten years we’ll all be sitting here with our brain implants”)
Back here in reality: Canada’s left-wing coalition will be ejected from power in the next election, that’s pretty well a forgone conclusion.
The US would be headed in that direction, provided the election in November actually takes place and isn’t rigged. The stakes are so high there, it’s hard to know what will happen. I once said that Donald Trump would be the penultimate President of the United States as we know them. Meaning, whoever came after him, would be the last President of a United States. We’ll see.
The public sentiment is overwhelmingly done with climate alarmism, wokeness, and cultural Marxism in general. The question now is, will this backlash and turning point be allowed to express itself peacefully and democratically? Or will it end up unleashing a more forceful backlash?
This is all part of the war between centralization and decentralization, which I’ve always said is, and will be, the defining tension of our era. This will transcend left vs. right, conservative vs. liberal.
The battle now is between people who want to decide things for everybody else, vs. people who want control over their own lives.
The Most Important Thing You Can Do
First – you have to help dismantle the norm that it is somehow unacceptable or immoral to reject the prevailing climate alarmism.
When Karen the co-worker goes off on a sermon in the lunchroom that “Pierre Poilievre has no climate action plan”, instead of internally smirking and looking forward to the next election, you have to speak up, right there and then, “Yes, that’s why everybody is going to vote for him, including me”.
This is important because, as we saw under COVID, the tyrannical regimens continued as long as normal people were afraid to speak their minds.
Nobody liked being arbitrarily divided into “essential” and “non-essential” workers and businesses.
Nobody liked wearing masks, sticking PCR tests up their noses or standing on the fucking dots. But everybody did it, because the first two doctors who spoke up about how stupid it all was, had their careers destroyed – and that set the trend for the next two years.
It was the forced vaccinations that finally put the public over the edge, and it took a near uprising by the #FreedomConvoy to finally turn the tide and put an end to it.
The coming Climate Authoritarianism will make COVID tyranny seem like a libertarian paradise.
In today’s landscape of internet connected everything, big data, and now AI, and soon, monetary Apartheid viaCBDCs, all the ingredients will be there for a technocratic authoritarianism that netzero and degrowth requires.
Your job isn’t to tell the government you aren’t on board with this: your job is to demonstrate to those around you that it’s ok not to be on board with it.
That also means you will have to be able the weather the consequences of not being on board with it.
My advice continues to be: strive for financial independence – if you have a job, start your own business on the side. If you already own a business, start, buy or invest in another one. Get yourself to the point where you can be fired, canceled, ridiculed and shunned and it not being the end of you.
Of course, that also means, if you haven’t already, start stacking Bitcoin. It’s the one monetary asset no government, no bureaucrat and no supranational entity can ever take away from you, that gains purchasing power over time and is in general, The Big Short on clown world we’re heading into.
* * *
My next e-book The CBDC Survival Guide: Navigating Monetary Apartheid will be out soon (honest), sign up for The Bombthrower mailing list and I’ll let you know when it drops – and get a copy of the The Crypto Capitalist Manifesto in the meantime.
Grab (GRAB) , the Singapore-headquartered “Everyday Everything App,” is Southeast Asia’s answer to Uber, DoorDash, Instacart, and Venmo — all in a single platform.
Best known for its ride-hailing and delivery services, the Grab app also offers a wallet feature that allows users to make payments online and in person, send money to family and friends, finance purchases over time, and even buy travel insurance.
In essence, Grab is (attempting to become) the go-to digital toolkit for everyday life in the eight countries in which it operates — currently, that’s Cambodia, Indonesia, Singapore, Malaysia, Myanmar, the Philippines, Thailand, and Vietnam.
The app has been called Southeast Asia’s answer to Uber, and, as of late 2023, Grab reportedly serves 35 million unique users each month according to the Business Times.
Much like Uber does in the U.S., Grab connects riders to drivers and diners to delivery people across eight countries in Southeast Asia.
Trading publicly in the United States on the Nasdaq exchange since its 2021 IPO, the company turned a profit for the first time during the fourth quarter of 2023 and shows no signs of slowing down.
Here’s what you need to know about Grab's features, its stock, and its ongoing quest to become Southeast Asia’s “one app to rule them all.”
How did Grab become the Uber of Southeast Asia? A short history of the app
Grab was born in 2012 at Harvard Business School, the brainchild of Anthony Tan (CEO) and Tan Hooi Ling (COO), both Malaysian nationals who earned their MBAs there the year prior. The pair launched their mobile app — then called “My Teksi” — using a $25,000 grant from the school along with an unknown amount of personal capital.
The purpose of the app was to connect taxi drivers with passengers via their smartphones in order to create a simple and orderly alternative to Malaysia’s then-chaotic (and sometimes unsafe, especially for female riders) ride-hailing environment.
In 2013, the company — by then called GrabTaxi — expanded, making its digital ride-hailing app available in the Philippines that summer, then in Singapore and Thailand before the year’s end. The next year, the company rolled out a fleet of 100 electric taxis in Singapore, expanded operations to major cities in Vietnam and Indonesia, and launched GrabBike, a ride-hailing service for motorbike rides.
Anthony Tan (CEO) launched grab with colleague Tan Hooi Ling (COO) in 2012 after the two graduated from Harvard Business School.
In 2015, the company launched GrabExpress as a package courier service. The following year, it rebranded (shortening its name to Grab and updating its logo) and introduced in-app messaging and translation for drivers and riders. It also created the GrabRewards program, through which users can earn points redeemable toward discounts on subsequent Grab services.
In 2017, the company launched GrabPay, its first financial technology offering, after acquiring an Indonesian payment company called Kudo. Next, it acquired Uber’s Southeast Asian assets and operations in early 2018, cementing Grab’s status as the dominant ride-hailing service in the region.
As a result of this acquisition, which included Uber Eats, Grab added food-delivery services to its suite of offerings, first in Singapore and Malaysia, and then in the remainder of its market before the year’s end.
As part of this deal, Uber received a 27.5% stake in Grab, and Uber CEO Dara Khosrowshahi joined the company’s board. So, the American-based ride-hailing and delivery giant now has a vested interest in seeing Grab succeed in its own market. Also as part of this 2018 acquisition, Grab agreed to go public by March 2023, a promise it kept with a little over a year to spare.
Business Insider reported the same year that Grab had become Southeast Asia’s first “decacorn” after securing more funding than any other tech startup in the region during the three years prior. (Unicorns are privately held companies worth more than $1 billion, while “decacorns” are privately held companies worth over $10 million.)
The company continued to make acquisitions in the fintech space, gradually expanding its in-app financial offerings to include money transfers, payments to merchants, microloans, insurance services for drivers and passengers, and buy-now-pay-later programs.
Anthony Tan (CEO) and Tan Hooi Ling (COO) are pictured here celebrating the company's 2021 IPO on the Nasdaq stock exchange.
By the time it went public on the U.S. stock market via a SPAC merger with Altimeter Growth Corp., the company had built a vast network of partnerships that allowed customers to hail car and motorbike rides, book travel, order food, pay for goods and services, send and receive money, and even obtain travel insurance policies.
In December 2021, Grab shares opened at $13.06 during the company’s first day trading on the Nasdaq, but they tumbled to around half that by the end of the day. Shares continued to fall, and for the next two years, they bobbed up and down in the $2.80 to $3.80 range.
In the fourth quarter of 2023, however, Grab moved into the black for the first time, posting a profit of $11 million on revenue of $653 million, up 30% from the 2022 fourth quarter.
So, what’s next for the Uber-backed “everything app?”
The market has known since late February 2024 that Grab became profitable during 2023’s final quarter and that it was initiating its first-ever share repurchase program (both of these are usually positives for a stock). That news, however, didn’t seem to do much to bolster the company’s stock price, which sat at around $3.16 then and hadn’t moved much by early April.
The company’s first-quarter 2024 earnings call is set for May 16, and any guidance the company issues on the call could be the catalyst that pushes the stock out of its limbo.
As of this article's last update, company insiders held about a quarter of Grab's stock, while institutional investors — including Morgan Stanley, Blackrock, Invesco, and Bank of America — held just shy of 55% percent. Short interest stood at 2.73%, indicating largely positive sentiment.
During the company’s last earnings call, CEO Anthony Tan said that Grab has grown to become the “largest on-demand platform in the region at a scale that is over 3x larger than [its] next-closest competitor.”
He also noted that, as pandemic-related travel hesitation has waned, the company’s “mobility revenues also increased by 26% YoY in Q4 and 36% YoY for the entire year, driven by an increase in tourist ride-hailing demand.”
During the call, Tan mentioned that the brand is increasing its focus on its travel segment. The travel business offers hotel booking and travel insurance services (more on these below), as non-local travelers tend to spend more than local customers in the markets where Grab operates.
All signs point to continued growth, but growth is expensive, so whether the company will continue to post profits in subsequent quarters will depend on how much it spends on acquisitions and partnerships vs. how much it leverages its current assets.
Because Grab operates in hundreds of cities across eight different countries, the services it offers vary by location. So, some of the features explained here may not be available in all markets.
For instance, Grab users in Vietnam, where motorbikes are ubiquitous, can order motorbike rides as a cheaper alternative to hiring a car, whereas in Singapore, where motorbikes are less popular, only car taxi rides are available.
Ride-hailing
Taxi-hailing was Grab’s first offering when it launched in Malaysia in 2012. The company’s mobility arm remains one of its most important, although it now ranks second to delivery in terms of revenue.
Functionally, Grab rides work much like those booked through Uber or Lyft in the U.S. Grab users can enter their destination and book taxi rides through the app with the cost shown up-front. Those willing to wait longer for a ride, share a car with other riders, or ride on the back of a motorbike can access lower fares.
All riders can view drivers’ details and ETA, and message drivers with instructions (the app can translate these messages if the rider and driver use different languages). Larger vehicles, pet-friendly cars, cars with booster seats for children, and luxury vehicles are also available at various price points.
Delivery services
Grab offers three types of delivery services: food, mart, and express. Together, these services account for more revenue than the company’s ride-hailing services.
GrabFood
Grab’s food-delivery feature is quite similar to DoorDash and Uber Eats. Customers can browse the menus of a variety of restaurants, ranging from street carts to fine dining, and order food for delivery, pick-up, or dine-in. Deliveries can be immediate or scheduled, and in-app discounts, coupons, and rewards are sometimes made available.
GrabMart
Grab’s mart delivery feature is similar to American apps like Instacart and GoPuff. Users can browse the wares of partner grocery, pharmacy, and convenience stores and order anything from food staples to toiletries. Deliveries can scheduled ahead of time or placed on an ASAP basis.
GrabExpress
GrabExpress is the company’s courier feature, which offers the types of services bike messengers provide in large American cities. A user requests a delivery and then hands off their parcel to a Grab partner, who immediately totes it to its destination, providing photographic proof of delivery upon completion.
This service can be used to send anything from a confidential single-page document to a 50 kg (110 lb) package, and all deliveries are automatically insured up to $500 (additional protection of up to $2,000 can be purchased for higher-value deliveries).
GrabPay allows users to pay for purchases online and in person using funds in the app's digital wallet.
Since around 2017, Grab has been expanding the financial side of its app via strategic acquisitions and partnerships with fintech companies. Its financial products vary depending on location, but most center around the GrabPay Wallet.
GrabPay Wallet
The GrabPay Wallet is a cashless payment system Grab customers can use to pay for Grab services, pay bills, send money to others, and make purchases online and in-person at merchants that accept GrabPay.
The GrabPay Wallet’s functionality is similar to that of Paypal or Apple Pay, and by using it, customers accumulate GrabRewards points that can be redeemed toward any of the services the Grab app offers.
Rider and driver insurance
Grab riders are automatically insured up to $20,000 in personal accident coverage whenever they hail a car or bike, and supplementary coverage of up to $100,000 can be purchased for an additional $0.30 per ride.
Grab drivers are also insured automatically up to $20,000 for accident-caused death or disability and up to $2,000 for accident-caused medical expenses.
Third-party liability insurance also covers drivers up to $200,000 for injury or property damage to others. Driver insurance also pays out up to $200 per day for 60 days of hospitalized medical leave or 14 days of non-hospitalized medical leave.
Travel
Grab also offers some in-app solutions for non-local travelers, although these are still somewhat limited.
Travel insurance
Grab users who are traveling can use the app to purchase travel insurance that covers things like medical expenses, delays, and lost luggage. Users enter basic information like their destination and trip duration, and the app provides an instant quote, with daily premiums starting at around $4.
Hotel booking
Grab users can book stays at millions of hotels directly through the Grab app, sometimes with Grab-exclusive discounts, earning Grab rewards as they do so.
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