There's a bit of a . . . survivorship bias here, despite the unfortunate name. People generally no longer die from diseases that we have eradicated, or can treat, control or cure, so they die more from things we can't cure yet.
Maybe the question is whether there is an illness out there that's impossible to cure or treat, but science doesn't look at it that way
@FaheemMitha exciting stuff, isn't it? In about a decade, we'll know much more about it
@FaheemMitha no, cancer cells differ from normal cells in quite a lot of ways. They do have different antigens, but, especially the more vicious types can even stimulate specific types of immune cells not to attack the malignant tissue
The treatments already available are a lot different than just nuking everything so that maybe cancerous cells die (that was like 60 years ago), but clearly we could do a lot better. For example, cancerous cells often divide at a crazily high rate, so they uptake a lot of glucose, and can't burn that properly, like when you get sore from strenuous exercise. Acid buildup leads to a lower pH in malignant tissue.
If you administer a drug that penetrates tissue better at lower pH, or is activated by a more acidic environment, then you've kinda sorta targeted the cancer cells. More recent drugs tend to have specific portions in their molecule so that they're either (1) only activated by enzymes inside cancerous cells, at least theoretically, or (2) match a receptor on the cancerous cells, so they uptake the drug at much much higher rates.
Even more recent drugs are biological drugs that target either receptors that are very highly expressed on cancerous cells, or are unique to cancerous cells, thus either deactivating them or activating the immune system to destroy them or both. Biological drugs have a long way to go in terms of specificity, especially given their potential to be much more specific than conventional drugs.
And there are specialized markers that latch on to receptors on cancerous cells, and glow during an operation, so that the surgeon can remove all cancerous tissue.
Pafolacianine, sold under the brand name Cytalux, is an optical imaging agent used in fluorescence-guided surgery.The most common side effects of pafolacianine include infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching and hypersensitivity.It was approved for medical use in the United States in November 2021.Pafolacianine is a fluorescent drug that targets the folate receptor alpha (FRa).
== Medical uses ==
Pafolacianine is indicated as an adjunct for intraoperative identification of malignant lesions in people with ovarian cancer...
Unfortunately, anti-cancer drugs are still some of the most potent toxins out there, and their very job is to wreak havoc in cells. So even if a drug is 10000 times more likely to go where it's supposed to, especially more susceptible cells and individuals and cells will suffer quite a lot of damage.
Another problem is they're sometimes not as specific as we want them to. Because conventional drugs are 'small' molecules, and there are a myriad of enzymes in the body, especially in the liver, you can't guarantee that, should you design a drug that is supposed to be activated only by an enzyme inside cancerous cells, the drug won't be activated by another enzyme in the blood or especially in the liver.
This is the case for cyclophosphamide, which is AFAIK still a major drug in most cancer therapy regimens. It was designed to be activated only in cancerous cells, by an enzyme than doesn't exist in normal cells. Turns out several microsomal enzymes in the liver metabolize it, and the toxic metabolites enter the bloodstream and cause adverse effects
@M.A.R. *poison, not toxin
@CowperKettle haha awesome stuff
Ah, I love the smell of pharmacology in the morning
@M.A.R. The medications they gave my mother appeared to do nothing whatever. The first one they tried targeted some hormone. And supposedly the tumor was hormone sensitive, but it still didn't do anything. Then we tried some other medication, all very expensive, and that didn't seem to do anything either. Then she got fluid outside her lungs (pleural effusion or something), we took her to hospital, she picked up a secondary infection, and she died there.
There was basically no testing of the tumor in order to target it. It seemed pretty stone age to me.
Of course my mother was 83, which probably meant that some treatments were off the table.
@M.A.R. What is the meaning of 'small' in this context?
@FaheemMitha I'm sorry to hear that. Under physiological conditions (meaning normal, as opposed to 'pathological') estrogen makes certain cells in the breasts and endometrium proliferate (just like testosterone does in the testes). Estrogen has a receptor. There are many ways for cells to go cancerous, some of which involve this receptor. Maybe a regulatory protein has mutated and is no longer functional, so the number of estrogen receptors skyrockets. Maybe more estrogen than normal is secreted.
Rarely, postmenopausal hormone replacement therapy is the culprit. Either way, the cell receives a very strong signal to proliferate. The cell is not removed by the immune system and develops into cancerous tissue.
In these cases, and cases similar to these, if you prevent that strong signal from making the cells proliferate further, you can control the cancer. Thus, a compound that looks similar to estrogen, and thus binds the receptor, but is different enough that doesn't initiate the signal, or initiates it weakly, can help. Tamoxifen is one such drug.
As long as the clinical diagnosis is correct, there is no need for biopsy to obtain a sample of the cancer tissue, because it's an invasive and stressful process.
For geriatric patients, many types of surgery are off the table. I don't know about the restrictions in administering anti-cancer drugs. And what I said is rather general as well; different cancer types and different cases demonstrate a wide range of drug resistances, potential for metastasis etc.
@FaheemMitha conventional or 'small-molecule' drugs are drugs we're familiar with: Administered by oral, sublingual, parenteral, ophthalmic etc. routes, they have a definite chemical structure which you can find out about with a Google, they have molecular weights around 500, very rarely more than 2000 g/mol.
@M.A.R. In my mother's case, it was approximately stage 4 when discovered, so probably hopeless anyway. But my main point is that I expected a rather more high-tech approach than I in fact experienced with regard to targeting the tumor.
'Conventional' is as opposed to biological, because biological drugs have different properties, and require special conditions for manufacture, storage, and administration. They're much larger molecules, and if you Google them, you'll get an inscrutable 3D model, similar to proteins. Antibodies have molecular weights of around 150000 g/mol.
@FaheemMitha well, all the science is embedded in the dull-looking pill, and the exact therapy regimen. The doctor's role is monitoring the effectiveness of the therapy, managing the side effects, and smiling and looking presentable
@FaheemMitha some can be tens of thousands of dollars per vial
Of course, this knowledge is outdated. As we get better at making them, and coming up with better drugs, we can drastically reduce the costs.
CAR-T and similar methods are very new. They're rapidly improving, and they require a lot of 'field experience' before they're fully incorporated as cancer therapies
For example, immunology is exploding as a field, and the lecturers are often young and energetic, while pharmacology often deals with drugs we have known for half a century, because you need decades to really trust most drugs
@FaheemMitha oh definitely. Of course, once I specialize in a field, I'm gonna forget most of it, except the stuff I like to revisit
I'm a year four student, and I've already forgotten more than I already know, even from these introductory courses
> The population of the United States had doubled in my lifetime, and the old simple world that I had known as a boy was gone. India was a reminder to me of what was in store for us all, a glimpse of the future. Trillions of dollars were spent to keep people breathing, to cure disease, and to extend human life, but nothing was being done to relieve the planet of overpopulation, the contending billions, like those ants on the rotting fruit.
@FaheemMitha nothing serious AFAIK, if you mean some sort of drug or therapy that quantifiably or reliably reduces the chance of getting cancer. Well, it's complicated.
Cancer often comes from faulty gene replication, and you probably can't help it. Every second, a lot of errors are made inside cells while copying/expressing genes.
The body makes heavy use of the oxygen atom (obviously), and oxygen has a tendency to form radicals, oxidizing agents and other sorts of very reactive compounds. Most cells in the body also contain machinery (supremolecular complexes) and molecules that convert these reactive byproducts of enzymatic activity to harmless substances like water. If they don't, and the cell is damaged, there's some possibility that it will gain the potential to become a cancerous cell.
Even then, T cells, the ones that kill, come and kill the cell (rather, tell it to go kill itself). There are dozens of checks and balances here.
> I wish I had the voice of Homer To sing of rectal carcinoma, Which kills a lot more chaps, in fact, Than were bumped off when Troy was sacked. ("Cancer's a funny thing", John Haldane)
One of these protective molecules are the reducing agents that prevent proteins from being oxidized. Glutathione is one of the main anti-oxidants of the cell. Vitamin C, for example, helps replenish the supply of glutathione in the cells, because Vit C itself is a reducing agent. Lycopene, some carotenoids, generally all those nice anti-oxidants in plants reduce the possibility of the depletion of glutathione.
Can you say though, that tomatoes prevent cancer? It's such a loose definition of 'prevent'. The best you can do is gather some data from a population that says tomato eaters get, I dunno, prostate cancer 10 percent less.
So we kinda already have all sorts of herbal supplements rife with cheap antioxidants that are marketed as preventing cancer or autoimmune diseases blah blah blah
> The TP53 gene is the most frequently mutated gene (>50%) in human cancer, indicating that the TP53 gene plays a crucial role in preventing cancer formation.[6]
And a huge host of genes that make this or that subtype of cancer aggressive, like CIC, which forms chimeric proteins with other genes to make tumors aggressive and resistant to treatment.
"Gene fancy-name on chromosome 13 is linked to CLL" "Deletions at the ass area of chromosome 20 lead to susceptibility to viral infections that increase the incidence of cervical cancer"
But these are rather . . . preliminary. Years away from suitable gene therapy, if it was ever funded
Then you have conditions that are prevalent in a large portion of the population that make one susceptible to cancer. Hyperplasia and neoplasia in one or more lobes of the thyroid gland are really common. Benign prostate hyperplasia is very common in men. Does it make any economical sense to have half the men in the world take these hypothetical cancer prevention pills? Probably not.
@CowperKettle for a lot of cancer types we do know these markers.
Current guidelines indicate that all people above 50 years of age undergo colonoscopy for screening of early stages of colorectal cancer. And it works wonders, but how many people are willing to undergo that?
It's amazing that it did not work for the first couple weeks, and just started working several days after a dose increase, and did that instantly. But if the vision deterioration is indeed caused by it, I would have to try a different drug.
Other people ramp the dose as high as 300+ mg/day, so it must be a rare side effect.
Another side effect was increased perspiration, but it was tolerable for the sake of a better mental condition.
The first-choice antidepressants increase only serotonin, and Venlafaxine increases two neurotransmitters.
Noradrenaline sometimes works to make a person more active.
Thus helping more than the usual antidepressants, but sometimes causing the loss of sleep.
So it's kind of try-and-see.
I did not expect it to work so powerfully, because a friend told me it was like eating chalk even at the dose of 300 mg/day, only with a slightly elevated mood.
Every person's reaction is different though.
Antidepressants fail to work in about 30% of patients.
@CowperKettle I believe that the central nervous stimulants unselectively increase the production of multiple neurotransmitters, but often at the cost of sleep.
@CowperKettle I'm aware that serotonin has something to do with depression. Lack of it helps to cause depression, or something. But I don't understand how that is connected to your eyesight.
@FaheemMitha regular? I don't think any clinical procedure requires endoscopy or colonscopy (which is worse) for follow-up. Colorectal cancer screening should ideally be done every 10 years or so.
@tchrist you have a family of anti-depressants called SSRIs (Selective Serotonin Reuptake Inhibitor), and another called SNRIs (Serotonin-Norepinephrine Reuptake Inhibitor). Both very commonly prescribed with more tolerable side effects.
They have a bit of specificity, due to both a mechanism I don't remember, and the arrangement of neurons that secrete these neurotransmitters
But yeah, they're overall very non-specific
You have anxiolytics that work on GABA receptors (GABA is an inhibitory neurotransmitter and decreases the overall excitability of the brain), e.g. Xanax
The abuse potential and LD50 (more specifically, how likely is an overdose to be lethal) are the main considerations regarding their adverse effects, so for most other adverse effects, there's a general attitude of "deal with it"
@M.A.R. Not exactly totally irrelevant but maybe far afield, but I just saw the movie 'Awakenings' about using L-Dopa (a dopamine precursor) to treat some very specific kinds of catatonia, and the way the movie made it seem it was like magic, these people had been 'awakened'. But at the end of the movie... well it wasn't clear but it wasn't a 'cure', they had to stop giving the L-Dopa because of side effects (?...it wasn't clear... did I say that?).
So I'm wondering what the current status of L-Dopa is.
@Mitch L-Dopa is unsurprisingly a dopamine agonist. The main indication is for Parkinsonism, where dopaminergic pathways in the brain have diminished activity. It's administered with carbidopa, because otherwise it would be immediately metabolized in the periphery and never reach the brain. Carbidopa is an inhibitor and substrate for peripheral DOPA decarboxylase, so levodopa can reach the brain and boost the dopamine pathways there.
AFAIK catatonia is a manifestation of some specific forms of psychoses. In psychosis, most areas of the brain have increased dopaminergic activity (alongside increased glutamatergic and serotonergic activity), but studies show some parts, for example certain nuclei in mesencephalon, if I'm not mistaken, have diminished dopaminergic activity, so levodopa is not the first choice for most (all?) types of psychoses but may be administered for catatonia
I dunno, psychosis treatment is a mess. Sometimes they try anything that works, just throw in drugs there, antidepressants, anticholinergics, lithium, etc. until something sticks
@FaheemMitha a colonoscopy is administered for diagnosis of certain diseases, and also the screening of certain chronic diseases. It's not regular though, people at most undergo colonoscopies every six months, I think
@Mitch anyway levodopa itself is kinda a safe drug, it can rarely cause severe hypotension but that's about it. Unfortunately, in chronic use, dopamine agonists can exacerbate or precipitate symptoms of psychosis, varying from certain involuntary movements to more severe behavioral issues. The reverse is also true: Dopamine antagonists are the main drugs used in psychotic disorders, and they cause or exacerbate Parkinson-like syndromes (such as nervous ticks)
Kinda like two ends of a spectrum. The reality is of course much more complicated, but it's generally like that
Well, WebMD is blocked so I can't check for other adverse effects of levodopa. I would need to consult a textbook, but that's booooring
@M.A.R. got it. the movie did hint that it can go both ways, repressing tics or exacerbating them considerably.
@M.A.R. I used the word 'catatonia'...I'm not sure if that was what they used in the movie (or original book) or if I just thought that's what it looked like from how the actors acted.
@M.A.R. It was made in 1990 from a book in the 70's about a psychiatric hospital in the 60's. It looks dated but I can't tell if it because the movie was good at the 1960's period decor, or if was just ... 1990's old.
Also, they really relied a lot on EEGs in the movie, and I realized afterwards that I haven't seen much of those lately and wonder if imaging (CT and MRI) has totally taken away the need for EEGs or at least eclipsed EEGs considerably.
@Mitch EEGs are still very important AFAICT. The biggest change since 50 years ago would be that most psychotic patients no longer require hospitalization for long periods, only during acute episodes due to draw withdrawal, or a suicide attempt, things like that.
We have since developed entirely new class of drugs that are more effective and with fewer side effects, but as I said we have a long way to go. Oftentimes the patients don't get better with monotherapy, so the doctor theorizes some based on the symptoms and tries another drug, then another, until one provides significant behavioral or mood improvements
There's also an aspect of psychotic disorders that has to do with cognitive impairment, which is a very active area of research. Most places in the brain become overactive, so how come the patient becomes cognitively impaired? For this cognitive impairment, a huge range of drugs can be administered, antidepressants, for example, until one drug seems to help the most
@M.A.R. *classes
EEGs are most important with regards to seizures AFAIK. Some drugs that affect the brain can worsen seizures, or even induce seizures. Monitoring that is best done with an EEG.
Seizures themselves, regardless of origin, are characterized by the appearance of EEG waves. And there are other applications too, like analyzing sleep patterns and wacky research stuff
So all in all I suppose brain activity is monitored best using EEGs.
If you don't have an anatomical change, CT or MRI won't do much good
MRI tends to be more expensive than CT, but it's a more versatile tool, often able to provide more contrast and fewer artifacts