Science: "Cancer disappeared!" news on early June 2022 (cancer journal club in the lab)

 A few weeks ago, many major news outlets reported this news, sensationally titled "cancer disappeared!".

The news was based on a report on New England Journal of Medicine (NEJM), published on 6/5/2022. The journal is highly regarded.

Link to the paper.  https://www.nejm.org/doi/10.1056/NEJMoa2201445

We picked up the paper for our journal club in the lab.

Background. 

(a) Immunotherapy reagent (PD1 blocker) has shown success in various cancers, including metastatic (stage 4) colorectal cancer. 

(b) PD1 blocker indicated particularly good efficacy on a subset of cancers with mismatch-repair deficient characteristic.

(c) Standard colorectal cancer therapy is initial treatment with chemotherapy drugs (combination of DNA damaging drugs such as fluoropyrimidine and platinum compound oxaliplatin), followed by chemoradio therapy then surgery. 

(d) But the response rate for the standard therapy is up to 25%. The current therapy comes with complications, toxicity and fertility challenge. Much to be desired.

In the report, the group in Sloan Kettering Memorial Cancer Center hypothesized that single reagent PD1 blocker could be effective in patients with mismatch-repair deficient, localized (stage 2 and 3) rectal cancers.

They enrolled 16 patients with mismatch repair-deficient rectal cancer and stated treatment with PD1 blocker every 3 weeks for 6 months.

 In the planning, (Plan A) if the single drug treatment work, no chemo or surgery, and (Plan B) the PD1 blocker treatment should be followed by chemoradiotherapy then surgery (=standard therapy).

They monitored the cancer at the start, 6 weeks, 3 months and 6 months. 

Amazingly, the cancer literally "disappeared" in 100% of 12 patients who went through the 6 months treatment of PD1 blocker. 

In all clinical monitoring parameters (imaging analyses with MRI, PET, endoscopy, digital examination, histopathological analyses on biopsy samples), rectal cancers were not seen. They did not even have to pull out the Plan B/follow up with chemoradio therapy then surgery.

If we point out something cautionary and less rosy, 

(i) mismatch repair-deficient colorectal cancers are about 5-10% of colorectal cancers. 

(ii) This is a phase2 trial with small size of white patients in single institute. 

(iii) If the cancer ever comes back or not in a long term remains to be seen.

(iv) They did not talk about the cost, but PD1 blockers are not cheap. 

Yet, the way cancer disappeared with only mild to moderate side effects if any was indeed newsworthy.

Cancer is a collection of many diseases. They reported a very effective way to deal with mismatch repair-deficient, stage 2/3 rectal cancers. Highly promising.

Cancer is "cured" like this. You can call it a trench warfare. By conquering one type of cancer at a time, we'd eventually have effective ways to "cure" many other types of cancers.

[For non-medical practitioners. gross alert]

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[Figure 1A from the paper. An example of "cancer disappearance" over time]

Life: Active shooter safety training 6/23/22

 Our Cancer Center was mandating active shooter safety training for the staff. 

This training was announced after a school shooting incident on 5/24/2022 in Uvalde Texas. With some mis-judgements and confusion causing delay in rescue attempt by the police, the incidence left 19 elementary school kids and 2 teachers dead. The shooter was killed, which offers a sliver of solace in the terrible incident.

There was another incident in Tulsa, OK, which was a shooting in hospital on 6/1/2022. A disgruntled and resentful patient shot and killed four people. Three were hospital staff including the patient's surgeon, and one was a "wrong place wrong time" bystander. In this case, the police acted quickly and the shooter killed himself before more harm was done.

In such emergencies, response can make a difference.

I attended a training session today. Campus police chief gave a well-organized 1 hour talk with a short video, "Run, Hide, Fight". As the short video summarizes the message well, I link it here.

  ["Run, Hide, Fight" posted by Ready Houston. Nicely educational.]

Active shooter situations have occurred in schools, hospitals, churches, shopping malls, movie theaters, restaurants, concerts, even in a military base. It happened in many public places, and not only in a "soft" target. 

Sickening, but it is the reality of 2022 America.

Training needs to be implemented, although I'd rather not be in an active shooter situation that forces me to use the training. 

Following the training, I checked out exits around the lab and the office to "run". Also checked out if there are suitable rooms/places to "hide". To "fight" with improvised weapons,.....there is a fire extinguisher right outside of office, maybe pens and scissors (look pathetic), some notebooks and magazines for light emergency body armor and....maybe this marble tiger from Pakistan? Ugh.

Seriously, I don't fancy throwing a bottle of sulfuric acid or hydrochloric acid in the lab. Might work better than a pen, though.

My worksite is a cross between school and hospital. School teachers and medical staff will have it tougher, as they may have to look after young students or immobile patients. 

Heck, I'd really hate it if I were in the situation.

Science: Innovation in medical science...what does it mean?

 The word "innovation" is highly regarded. But what does "innovation" really mean in medical science?

Check out Shark Tank or something. 

We have seen a bunch of stuff trying to sell themselves as innovative, but did not fly. We have seen "innovation" for the sake of novelty, but nobody picked it up. (Come to think of it, they still can be good niche products for the fans. But the word "innovation" implies broad and big coverage). Perhaps, the notion of "innovation" is not understood correctly, not defined properly, or is just overrated?

In a government grant section, we scientists need to explain "innovation" of our research project. That made me think what innovation really means.

If we look back in the history, innovations were Dynamite, T-ford car, Walkman (Sony), ipod (Apple), Penicillin, guns, smartphone, vaccination, etc. 

mRNA vaccine is a major improvement in vaccination. You can debate if mRNA vaccine counts as a true "innovation".

Common to all "innovation" is that they all changed previous ways, status quo at the time, to a new way while solving problems with old ways. Innovations change our ways of doing things.

It sounds like talking from the result, I know. But in retrospect many innovations look like well-designed from the beginning, even if they actually were products of serendipity.

When I apply this notion of "innovation" to science, to be innovative, outcomes of our medical research should change current medical practice for the better in a big way.

I've worked in cancer chemoprevention research field for 15 years and have developed some familiarity in the field. There are many chemicals, dietary compounds, etc, that actually can reduce cancers in animals and likely in humans.

But the body of knowledge has not been fully translated to current medical practice. In fact, cancer prevention is rather poorly practiced. We are only beginning to test the approach on a small segment of patients with well-defined genetic cancer-predisposition (like Lynch syndrome with known genetic mutation that will increase colon cancer risk), or well-defined high risk factor (like pancreatitis for developing pancreatic cancer).

In these cases, applying cancer prevention measures by itself is innovation, compared with current practice of preemptive surgical removal of colon (which comes with likely QOL decrease) or of careful monitoring and doing nothing.

Anyhow, to define innovation, we need to know current medical practice. Then we need to apply our science and research to improve current practice for the better (hopefully in a big way).

Sure, "innovative" research tools like cancer genome sequencer have changed medical practice. The sequencer enabled oncology clinicians to identify gene mutations that are likely driving the cancer, so that the clinicians can pick a promising drug. Yet, clinicians changed their ways as users of the new tools. 

Basic researchers need to think what will bring next innovation and what will be accepted/useful to the users. 

True, many Nobel prize-level discoveries were ahead of time and had a long time collecting dust on the shelf before new users recognized the value and made them to innovation. Yet, we may need to keep putting forth the best designed outcomes.

Dance: "Bella Ciao"

 While browsing YouTube, I came across a video with a song with very "sticky" tune.

The song is called "Bella Ciao". Apparently it has been very popular in Europe for a few years (actually, in the US it was rare to hear the song).

Quick search showed; 

(a) originally the tune was a folk song in Northern Italy, 

(b) the song was used as anti-fascist song by European Partisans in mid 20th century, and 

(c) made very popular in Europe by Spanish TV-Netflix series "La casa de papel (Money Heist) "(2017/2019-2021) as its sub-theme song. The drama series was about two heists by a group of robbers targeting big national institutes (Royal mint of Spain and Bank of Spain). They used the spirits of the song as anti-authority, as the robbers go against the national police and security forces that are not afraid to kill the robbers. 

I checked out a few clips, and they looked good. The clip of the Professor and Berlin (two main characters. They go by code names) singing the song over dining table was quite powerful.

The original song has either wide fluctuation of tempo from slow to fast, or goes fast. As a dance song, it is challenging (may be polka?).

But due to the popularity, there are so many versions found in YouTube.

For dances, Samba/ballroom Latin version, and Tango/milonga version, can be found.

[Milonga version of Bella Ciao] (not my video, for disclaimer)

Like the musical interpretation with fast footwork on '45-'49

Last night I talked with our Tango DJ David and he added the song to his computer. We may be dancing to it in upcoming milongas.