A future addition to the hallmarks of cancer may be the acquired plasticity associated with tumorigenesis, or in other words the enhanced ability of a tumor (or clonal population) to quickly adapt and respond to therapeutic interventions, or other insults, through genetic mutations, signaling, and modulations of differentiation status, etc relative to non-transformed cells. 

I personally work on Cancer Epigenetics of how environmental factors can change the normal/stem cell epigenome towards a more cancer specific epigenome, and have good reason to strongly support the notion that Epigenetics needs to be included. (or Environmental factors other than inflamation as well). Secondly, wound healing and mechanical stress stimuli or general Stress stimuli probably can be more of an inclusive term towards various environmental insults. 

I just feel that stress must also be laid on the autocrine action of factors  secreted by the cancer cells themselves, other than mediating cross-talk (paracrine action)with other cellular populations in the microenvironment which has been debated a lot in both versions of the landmark review.

A future addition to the hallmarks of cancer may be the acquired plasticity associated with tumorigenesis, or in other words the enhanced ability of a tumor (or clonal population) to quickly adapt and respond to therapeutic interventions, or other insults, through genetic mutations, signaling, and modulations of differentiation status, etc relative to non-transformed cells. 

aberrant mitosis

replication stress (though that could be under genomic instability)

Cancer cell demonstrate an acidification of extracellular pH and alkalinisation of intracellular pH such A - Reversed pH gradient could be an emerging Hallmark....

I agree with Erik Martin. Although a basic biological phenomenon, I definetively think that tumor plasticity and heterogeneity should be considered a major hallmark, at least in solid tumors. I would say that intratumoral (and in particularly metastatic) heterogeneity is the major challenge in the treatment of metastatic disease.

Dear John,

one hallmark of cancer cells, is the onset of replication after mitosis, during the G1 phase. In extreme cases as in ALL-1 leukemic cells, a G1 phase is lacking completely and onset of mitosis shortcuts the cell cycle.

Another hallmark ist the overexpression of Switch genes, i.e. HOX genes.

Wtih sunny wishes

Isolde

Dear John,all hallmarks of cancer cells listed are correct.But I would like to include the emotional status of the patient

The attached commentary outlines why I am skeptical about the Hannahan & Weinberg version of the hallmarks of cancer. The essence of my argument, which merely repeats what is stated in pathology textbooks,  is that a tumor that does not invade or metastasize is known as a benign (non-cancerous) tumor. Benign tumors are known as such because they are not prone to kill the patient, as in most cases they can be removed by surgery and do not recur. Hence, the hallmarks of cancer are, by definition, the abilities to invade and metastasize. All other features cited by Hannahan & Weinberg are shared with benign tumors. Please let me know if I have been misleading myself.

Teleomeric disintegration and epigenetic dysregulation should not be left out as well.

in support of reversed ph gradient as a hallmark:

1.Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression.Nat Rev Cancer. 2011 Aug 11.

2.Roberto B, Giancarlo R, Roberto M, Fabio A. Intracellular and Extracellular Tumor pH Measurement in a Series of Patients With Oral Cancer. Journal of Craniofacial Surgery, 2007; 18: 1051-1054.

3.Castaing M, Loiseau A, Dani M.Designing multidrug-resistance modulators circumventing the reverse pH gradient in tumours.J Pharm Pharmacol. 2001 Jul;53(7):1021-8.

Many more features can be included indeed. However, the real challenge to evaluate the cancer hallmark idea is at the conceptual level.

We have recently addressed this issue.

See: Evolutionary mechanism unifies the hallmarks of cancer

http://www.ncbi.nlm.nih.gov/pubmed/24957955

Any comments?

Dear John,we can complete  the hallmarks of cancer, including the lost of  quality of life influencing the genomic instability

I would like to add the term Entosis and Cannibalism ..as an additional  hallmark of cancer 

I would like to add that there's a study was published in 2014 about the role of metabostemness Activation

http://journal.frontiersin.org/article/10.3389/fonc.2014.00262/full

Yes Suresh!

I fully agree.

The attached articles could convince some "sceptic" ones.

I recently posted a question on RG about entosis inducers, but I did not collect "many" responses ...

Best regards

Robert

Dear all:

The 1971 War on Cancer was fought following the strategy outlined by H&W. In 2014, both DH and RAW, admitted having lost that War. The 2016 Cancer Moonshot is also based on the HoC strategy. One wonders where is that this Moonshot is going to land...

There is another way of thinking though (see below).

Carlos 

[Sonnenschein C and Soto AM 2013 The aging of the 2000 and 2011 Hallmarks of Cancer reviews: A critique. J. Biosci. 38 651–663]

DOI 10.1007/s12038-013-9335-6

Well said, Carlos!

More comments on the hallmark concept of cancer can be found in my recent book:

Debating Cancer: the Paradox in Cancer Research

http://www.worldscientific.com/worldscibooks/10.1142/8879

The introduction chapter is attached. 

Henry

http://www.worldscientific.com/worldscibooks/10.1142/8879

http://genetics.wayne.edu/heng/lab/Home.html

THANK YOU, HENRY! I'll read your Intro soon.

Best,

Carlos

Dear Carlos,

I already red with great interest "some times ago" your article about "revisiting the hallmarks of cancer" ... I cite your article in three "not so bad" "in process" reviews ...

Dear Henry,

I will read with more than great interest your book!

"However", Dear Carlos and Dear Henry, let us beeing "practical" and not "so usual "other-than-me" scientific "criticizer" ... (this is a sentence that I translate from French ...)

Would you be so kind, EACH OF YOU, in indicating ONE CANCER TARGET on which you take a bet, not in the H&W review, and indicating us WHY we no more than 5 lines (RG format) and 2 actual scientific references (i.e. research articles).

Thank you so much for your attention, and once again, pardon me for my foor French-translated English (or should I say "looking-like English),

Robert

Cher Robert:

If, as you state, you've read our papers, you may have been able to noticed that cancer is not a "cell-based" disease. Cancer is a "tissue-based" disease. If, on the other hand, you've read where H&W were in the XXth century, you may have discovered that in 2011 they somehow discovered that cancer happens to people in organs (tissues) and not in cells. Following your suggestion in "no more than 5 lines (RG format)" D'accord? 

Pas d'accord du tout Carlos (in somethink like English: Not at all agreeing with you).

First, I "appreciate" "more than moderately" when someone begins a scientific argumentation by "if ... as you state ... you have read our papers ..." ..

Your profile and mine on RG seems to indicate that I do not actually need this kind of response ... even if your RG profile seems to indicate that you are a "heavy weight" ...

Are you feeling yourself a little bit "unconfortable ... concerned" by my previous message?

Now, I propose that we leave as scientists such boring Q&A games .. and actyually entering something looking like science for our next RG Q&A discussion (knowing that young scientists are interested by scientific discussion).

If you want to pursue a "less scientific discussion" we can organize a skype chat ...

The H&W review is a very comprehensive REVIEW (and not a "theory") on the most PUBLISHED hallmarks of cancer ... This review relies on a synthesis of syntheses of syntheses ... about thousands of articles published in this domain ... Am I understanding the point you address: did H&W made a wrong analysis of the literature?

As someone who pretend to be a scientist (I am speaking about me ... and I now that this assertion is very arrogant from py part), I have to humbly admit that I have some problems to understand HOW SUDDENLY A WHOLE TISSUE BECOMES A CANCER ...

I am aware of some articles that have been published "just some years" before the very nice review by H&W ...  but also some years before the structure of DNA has been published ... leading to the "delivery" of a Nobel Prize ... Have you read the attached articles ?

These are very nice articles about TISSUE ORIGIN of cancer ... but a little biv older than the articles reviewed by H&W ...

THUS, I am still waiting from you THE precise target(s ==>?) you propose to take into account in "your" combat against cancer ... ==> five lines and 2 scientific references (i.e. not reviews ...).

A bientôt mon cher Carlos ...

Robert "Bobby" Kiss

PS: for some of the RG members who will continue to follow our (my own estimation) boring and sterile discussion ...) I am attaching the H&W review (2011) ...

Maybe actually, we must talk about the sepcific hallmarks of each cancer, not in general like Hanahann and weinberg in their review.