The core of this work is novel; highly valuable. Although this work is carries by new investigators into the field yet it will re-conceptualize our current understanding of tumor biology. Therefore, work should be encouraged and published, urgently. However, if this article is met your criteria of publication, few comments should be taking into consideration prior publication:

- It need abstract.
- This work should be re-edited by highly specialized person in the current field.
- I do notice that there are (10) references are cited but only (3) of them are mentioned in the text.
- According to this definition, each tumour must be definitely malignant by histopathology, each must be histologically distinct, and the possibility of one being a metastasis from the other must be excluded.

Also, the same tumor characterized by clonal heterogeneity. Most probably should due to temporal spatial configuration.
- It might have the ability to control growth and division of other cancer cells by sending inhibitory signaling which can only affect mutant receptors within the cancer cells that originated from different tissue (another primary tumour).

If these primary tumors develop into secondary, what are relationships between each secondary tumors and opposing primary tumors? Or among secondary tumors in compare to what happened with their ancestors? Moreover, what are interactions of secondary tumors with corresponding and opposing primary tumors? If not clear answers of such interactions, these questions should be included into manuscript as opened questions part to increase the consistency of this article.



- It is well established cancer at final stage, exploits and harness human and/or animal bodies and most of biological systems are become vulnerable to develop tumor (system collapse). So, how do author differentiate between primary tumors initially and that are developed after system collapse, especially authors have sentence describe cancer as opportunistic diseases?

- But in this case the growth pattern will be in slow rate and will hence increase the patient's survival, thus considering the immune system as third party in the relationship dimension

The following article should be cited; because it represents immune system as third party" "Tumor acidity as evolutionary spite"; Alfarouk et al. 2011, Cancers.

- This theory explains that although the patient might have the underlying genetic factors and environmental stress to grow multiple types of primary tumour, still it remains as a rare condition.  Second primary tumour will only be able to appear after treatment or removal of the first one, as it is suppressed by the inhibitory signaling which produced by the first primary tumour

Do all tumors in a competition?

- Evaluation of hypothesis:

    In one hand, although it looks like formal proposal yet this part should be re-edited as qualitative type of article. On the other hand, even original research article represents a proposal of future project(s).
    I do recommend Professor Carlo C. Maley (Carlo.Maley@ucsf.edu) at Helen Diller Family Cancer comprehensive Center, UCSF as further reviewer of this highly valuable topic. He is an expertise in analysis of competition among tumors.

- Also we can put pseudo barrier such as nitrocellulose paper to guarantee the exchange of inhibitory signals and to avoid cannibalism.

The term of cannibalism should be defined very well and I do recommend two recent articles that should be cited here:

    Evolution of tumor metabolism might reflect carcinogenesis as a reverse evolution process (dismantling of multicellularlity); Alfarouk et al. 2011, Cancers.

    TM9 and cannibalism: how to learn more about cancer by studying amoebae and invertebrates; Fais et al. 2011, Trend in Molecular Medicine.

We find that between the cancer formation stage and symptoms appearances there are many events that occur within the body. When the body contains the underlying genetic mutation together with environmental factors, this can allow many types of cancer to develop.

The following article should be cited:

    Figure (6) of: Why do tumors have high aerobic glycolysis? ; Gatenby et al.  2004, Nature Reviews Cancer

    "Carcinogenesis as evolutionary and ecological process" Merlo et al. 2006, Nature Review Cancer

Cancer has strong ability to use the surrounding environment to guarantee growth and survival

Further articles should be cited:

    "A microenvironmental model of carcinogenesis";  Gatenby et al. 2008, Nature Reviews Cancer

    "Of cancer and cave fish"; Gatenby 2011, Nature Review Cancer

    "Proton dynamics in cancer" Huber et al. 2010, Journal of Translating Medicine

     "Hallmarks of Cancer: The Next Generation" Hanahan et al. 2011, Cell

I hope these very simple comments will enrich and refine this novel work.

Best Wishes,

Khalid
Khalid O. Alfarouk, M Pharm
Department of Evolution of tumor Metabolism and Pharmacology,
Hala Alfarouk Cancer Center
Khartoum - Sudan