Fight against cancer: As immunotherapy hopes fade, two new studies hold out hope

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Published: April 1, 2017 2:47:14 AM

Towards the end of February, a study published in the British Medical Journal generated a lot of buzz. A review of 204 earlier works on the subject, it found that obesity is strongly linked to 11 different cancers.

British Medical Journal, Cancer Research, BMI, Body Max Index, risk of cancer, immunotherapy, immune cells, Salvador Aznar Benitah, lung tumoursTowards the end of February, a study published in the British Medical Journal generated a lot of buzz. A review of 204 earlier works on the subject, it found that obesity is strongly linked to 11 different cancers.

Towards the end of February, a study published in the British Medical Journal generated a lot of buzz. A review of 204 earlier works on the subject, it found that obesity is strongly linked to 11 different cancers: colon, rectum, endometrium, breast, ovary, kidney, pancreas, gastric cardia, biliary tract system and certain cancers of the oesophagus and bone marrow. Ninety-five of the 204 studies reviewed by scientists at the International Agency for Research on Cancer were analyses of obesity’s links to cancer using measures such as body mass index (BMI)—of these, 12 offered strong evidence of a positive correlation. With increase in BMI, the risk of cancer, too, shot up. Every 5kg/m2 increase in BMI caused the risk of colorectal cancer to go up by 9% among men. The risk of developing biliary tract cancer shot up by 56% for every such increase.

Cancer Research UK projects nearly 700,000 cases of cancer by 2035, linked to obesity. Much of this cancer burden will be concentrated in low- and middle-income countries, including India. A study published in Lancet shows a clear trend of rise in obesity here since 1975—while the country was ranked 19th for obesity among both men and women in 1975, by 2014, it was ranked 5th and 3rd, respectively. The just published National Family Health Survey found that the incidence of obesity has doubled in the decade between 2004-05 and 2014-15—from 21% of the population to nearly 40%. Thus, the biting irony that the country with the largest number of underweight individuals could be facing a crushing obesity-related cancer burden—as per one estimate, only 15% of the country’s population has an annual income that is above the baseline cost of cancer treatment.

Without cutting edge cancer research—especially on affordable therapy—the obesity problem gets compounded. Note, obesity and income have a complex, messy relationship. While the poorest in India are likely to be underweight, those in rich countries like the US are more likely to be obese—of course, with variations across race and sex. Developments in immunotherapy over the past few years made it seem like the prosaic silver bullet—it would cost a fraction of the conventional therapy. Which is why, when patients undergoing immunotherapy trials—the patients did show some signs of remission—started coming down with severe side-effects, the hope of a cheap cure was crushed.

Juno Therapeutics scrapped the trial of its genetically-engineered immune cells that were being used to fight cancer after five of the patients in the study died—the regulator had initially halted trials after three patients died, but later allowed it to resume. However, the last two deaths sealed the fate of the study, and the immunotherapy door is closed for now.

Two recent developments in cancer research, thus, assume a great deal of significance. Salvador Aznar Benitah of the Institute for Research in Biomedicine at the Barcelona Institute of Science and Technology in Spain and his colleagues, in mice studies, have identified a fatal weakness in the cells that mediate the spread of cancer: a total dependence on specific molecules to power their invasion. A cancer cell requires a great deal of energy to dislodge itself from its original site, swim through the bloodstream and lay siege on a different site in the body. The study by Benitah et al—published in Nature—found that amongst the cancer cells, the seed cells (that cause metastasis or spread of cancer in the body) expressed high levels of a molecule called CD36, that helps them absorb lipid molecules from their environment.

The researchers found that certain antibodies blocked CD36. This inhibited metastasis although it did not affect the incidence of primary tumours. Though the team is working to develop these antibodies for clinical trials, the researchers believe they are still some years away from it.

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Another research—the findings were published last month in Science—challenges our understanding of cancer fundamentally. Bert Vogelstein, a geneticist at the Sidney Kimmel Comprehensive Cancer Center, and Cristian Tomasetti, a mathematician at Johns Hopkins University in Baltimore, Maryland, in an earlier research, had found that the incidence of cancer was strongly correlated with the number of stem-cell divisions in an organ—stem-cell divisions in the brain are rarer than in the colon/rectum and correspondingly, cases of cancer of the brain were less common than colorectal ones. Carrying forward from there, they found, on the basis of mathematical models, that nearly two-thirds of the mutations behind cancers are caused by errors during DNA replication in cells.

Very few cancers are inherited (5%) and it is difficult to prevent them by making appropriate lifestyle choices—environmental factors contribute up to 35%. The study doesn’t contradict the fundamental epidemiological finding that 42% of cancers are preventable. But it does mean that the emphasis on environmental factors for most cancers may need a relook. The researchers calculated the relative contributions of the environment, heredity and DNA-replication errors to cancer mutations and found that while the contribution varied between types of cancers—environmental factors were behind 65% of certain lung tumours, for instance, while replication errors accounted for 35%—replication errors acoount for 66% cases in 32 different types of cancer.

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