Thursday, October 29, 2015

Important Breakthroughs In Cancer and Ageing

Personalised medicine with mTOR inhibitors and Telomerase modulators may serve as important breakthroughs in medicine. May be it can fetch more attention of organisations like Cancer Research UK, NCI and other funding agencies help in fighting Cancer and Ageing related problems.

mTOR is nutrition driven pathway. Dietary restrictions causes down regulation of mTORC1 activity.  Hence, targeting it with its inhibitor may help in providing anti-ageing and anti-cancer effect as shown in figure below.

It shows effect mTORC1 effect on longevity.  A cancer cell needs lot of energy because of its increase growing rate. Inhibiting mTORC1 with specific inhibitor helps in providing longevity.

Scientific paper mTOR and longevity can be accessed from here

According to Peto's paradox, chances of acquiring cancer is more in humans compared to large animals like elephants or whale even though these big sized animals have large number of big sized cells compared to humans.

Metabolic perspective of Peto's paradox and cancer  can be accessed from here

It's observed that small number of cells divide faster than big sized cells. As a result there are chances to acquire large number of genetic errors in rapidly dividing small cells. And these errors simply keeps on accumulating due to cell division. These accumulation of errors leads development of cancer. Moreover, with every cell division Telomere located at the end of DNA also keeps shortening. So basically with every cell division a piece of information is lost due to DNA damage. Telomerase enzyme helps in prevention of this loss and maintains the Telomere length. This in turn helps in maintaining the original length of DNA and prevents chromosomal shortening.

Details of this basic biology can be visualised in following Youtube video.
Basic function of telomerase.

Identification molecules which can increase synthesis of telomerase has been of prime importance.  These agents can also help in reversing ageing or may be useful for cancer prevention. Understanding of how telomerase works can be seen from a video of famous scientist Prof. Michio Kaku.

Friday, October 23, 2015

Ageing-Cancer dependency

Cancer is basically defined as uncontrolled multiplication of cells.  On the other hand, ageing is characterised by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death.

Cancer is one of the age related disease. The chances of occurrence increases with age as reported by Cancer Research UK, Centre for Disease Control (CDC) given graphs below

For more info click here

For more info click here

These tables clearly shows relation of ageing and cancer in clinical scenario. 

At cellular level relation of cancer and ageing can be visualised from the following image. As we know that cells in cancer condition grows faster hence they also catch up to the ultimate fate of death faster as compared to normal tissue. 

During normal ageing, stem cells accumulate damage and subsequent stress-dependent changes (for example, de-repression of the CDKN2a(INK4a/ARF) locus or telomere shortening). This leads to the increasing abundance of senescent cells (large blue cells) within differentiated tissues. Incipient tumours, arising directly from stem cells or from more committed cells, undergo rapid proliferation (small red cells). These pre-malignant tumour cells rapidly accumulate damage, in part owing to the presence of oncogenes, leading to a higher proportion of tumour cells becoming senescent (small blue cells). Tumour progression to full malignancy is favoured when tumour cells acquire mutations that impair the senescence program (for example, mutations in Trp53 or CDKN2a).

Biology of ageing-cancer relation is accessible here

Most commonly explored pathway for the treatment of ageing and at the same time cancer is m-TOR. I believe it is a wonder pathway for treatment of variety of other age related diseases. 

Moreover, this pathway serve as link between cancer and ageing. So inhibiting m-TOR not only stops cancer multiplication but also helps in increasing life expectancy of cells. It is ironical to say that inhibition of m-TOR helps in inhibiting two different ends of life viz. cancer (symbolises uncontrolled cell division) and ageing (symbolises death). 

Scientific paper for correlation of mTOR with age related disease can be downloaded from here

Hence, personalised cancer medicine by Pathway Pharmaceuticals and Insilco Inc. will help in developing newer strategies of increasing the life expectancy of not only cancer patients but also other individuals suffering from age related diseases.