Cancer Immunotherapy – Nature Reviews Genetics

Cancer touches almost everybody’s life. Here in this playlist you can watch a comprehensive summary about molecular and cellular mechanisms involved in cancer biology. Based on this knowledge, various new approaches for treatment is now on the agenda. Some have already showed considerable success.

Advances in cancer therapy comes from a number of cutting edge studies and projects including genomics, antibody research and metabolic understanding of cancer cells. The Cancer Genome Atlas project has been revolutionary in understanding the genomic landscape of cancer. Major Human cancer types has been sequenced and suspected mutations have been cataloged. Antibody based immunotherapy drugs that bind to diseased gene products use the information from the Cancer Genome Atlas. The seminal research article by Georges Köhler and César Milstein published in 1975 marked an important milestone in the history of antibody research. Köhler and Milstein described for the first time how monoclonal antibodies of a predefined specificity could be produced.

How antibodies can bind an almost limitless variety of targets was a big unanswered question. In their seminal 1980 paper which led to a Nobel Prize in 1987 Susumu Tonegawa and colleagues described gene recombination in B cells.

Using monoclonal antibodies drugs such as Tagrisso (Osimertinib) by AstraZeneca targets specific mutated gene products selected from the genome atlas. The drug binds irreversibly to epidermal growth factor receptor proteins (EGFR) with a T790M mutation. Tagrisso also binds to EGFR with a L858R mutation and with an exon 19 deletion.

At least eight mutations in the EGFR gene have been associated with lung cancer, a disease in which certain cells in the lung become abnormal and multiply uncontrollably to form a tumor. Nearly all these EGFR gene mutations occur during a person’s lifetime and are not inherited. Moreover these mutations only occur in cancer cells. Other genetic, environmental, and lifestyle factors also contribute to a person’s cancer risk. For lung cancer, the greatest risk factor is being a long-term smoker.

Somatic mutations in the EGFR gene most often occur in a type of lung cancer called non-small cell lung cancer, specifically a form called adenocarcinoma. These mutations are most common in cancer patients who have not smoked.

Most of the somatic EGFR gene mutations associated with lung cancer have a deletion in a part of the gene known as exon 19 or change DNA building blocks (nucleotides) in another region called exon 21. These changes in the gene result in a receptor protein that is constantly turned on. As a result, cells are signaled to constantly proliferate and survive, leading to tumor formation.

Lung cancers with EGFR gene mutations tend to respond to treatments targeting the signaling molecule epidermal growth factor (EGF). EGF conveys the signal for cancer cells to constantly grow and divide. A drug developed in Cuba CIMAvax-EGF targets EGF with monoclonal antibodies. CIMAvax is undergoing trials in Japan, Europe, and the United States. It is being used together with Opdivo, another EGFR blocker.

Immune checkpoint inhibitors of PD-L1 (programmed cell death – 1) also employ antibodies.

Scripps Institute researchers have managed to develop a variation of the CRISPR technology called RIBOTAC that guides a natural RNA degrading enzyme to a microRNA associated with breast cancer. The preliminary results have reported that the approach is effective on triple negative breast cancer. This is a very radical approach compared to other cancer treatments since the system uses a naturally occurring enzyme RNAse L to attack cancer.

Large animals are expected to develop cancer more often than small bodied animals since they have more cells that can mutate. This is known as Peto’s Paradox. Genome sequencing projects comparing entire animal kingdom with one another have revealed many interesting similarities and differences. Elephants have roughly 10 times more cells than Humans yet they get less cancer. A gene called p53 known to suppress tumor formation is present in 40 copies (20 from each parent) in elephants. This gene copy number is limited to two in Humans. Large animals therefore must have evolved tumor supressive cancer surveillance systems in order to achieve such large body sizes.

Increased carbohydrate intake is a hallmark of neolithic period. However today our intake of carbohydrates consist of highly refined and easily digestible forms such as high fructose corn syrup. There’s a relationship between sugar and cancer.

relationship between sugar and cancer

Cancer cells are power hungry and have a massive affinity towards glucose.

Warburg Effect

Metabolic