Saturday, August 20, 2016

Fighting Drug Resistant Cancer Using Immuno Therapy

Cancer is a notorious medical anomaly that often gets resistant to chemotherapy. Hence, newer methods are constantly being explored for fighting against it. List of Commonly Used Chemotherapy and their potential side effects are listed in my previous blog. Usually, these drugs
are given in combination to fight cancer at molecular level.

Cancer can be classified on organ system level and molecular level. For eg. breast cancer is a carcinoma of breast tissue that is different from brain tumor, pancreatic cancer and other cancer types. Breast cancer also shows perturbations in expression of variety of receptors and proteins. Hence, it can be  classified further as

i)    Basal Type or Triple Negative
ii)   HER2 positive breast cancer
iii)  Luminal A
iv)  Luminal B breast cancer cases

Similarly, most cancer shows variation in the expression levels of genes and their respective proteins. Hence targeting specific molecular pathways on a personalised level has been the focus of the cancer treatments and research.  There are antibodies been developed to fight most cancers like breast cancer, melanoma and others. Antibodies work via different mechanisms for e.g. anti-HER 2 antibody mechanism is shown in following video

Mechanism of Pertuzumab and Trastuzumab in HER-2 positive breast Cancer

In the present blog we will discuss about the various immuno targeted therapies that are been developed to fight variety of cancer. Cancer immune therapy with mono-clonal antibodies is recently explored extensively for cancer as mono or in combination with conventional small molecular inhibitors.
It is been noted that under normal circumstances genetic mutations in cancer cells present as an antigen to human immune system, which causes development of antibodies that prevents the development of cancer. However, constant evolution of cancer cells causes failure in the immune defence mechanism leading to development of cancer and also causes failure in chemotherapy. Cancer immune therapy is been developed that prevents immune regulatory pathways that causes activation of T cell. Some times cancer cells suppresses T cells via. activation of immune checkpoints like CTLA-4 and PD-1. Monoclonal antibody causes blockage of these check points and renders cancer preventive immunity, which provides a desired anticancer pharmacological response. List of monoclonal antibodies used for the cancer therapy is covered in my previous blog post about "chemotherapy against most common type of cancer". Detailed mode of action of immunotherapy against melanoma using check point directed inhibition is shown in following video.

Immunotherapy Basics and Use of PD-1 and CTLA-4 blockade by Antibody

Inspite of the fantastic strategy to kill cancer cell by boosting human immunity; there are reports of immune therapy resistant cancers. These are mostly formed as the monoclonal antibodies fails to provide protection against activation of concomitant multiple pathways that helps in cancer proliferation.  In order to boost effect of monoclonal antibodies they are mostly given in combination with small molecule inhibitors. Insilico Inc. has come up with a unique method to boost the effect of currently used monoclonal antibodies for cancer therapy.

Insilico Inc. is a computational company based in John HopKins university. They are known for developing computer based strategies for fighting ageing and cancer. One of the ongoing work at Insilico Inc. is focused on measurement and analysis of perturbations happening in the cellular pathways in patients that gives positive or negative response to the checkpoint inhibitors. This novel strategy is aimed to provide potential inhibitors that may help in boosting the pharmacological response of monoclonal antibodies. 

These 12 leads are the part of DeepPharma AI developed by Insilico Inc that alsolarge number of molecules that are predicted to be effective against age related conditions like CVD, CNS. Public sector academic groups and private sector organisations can contact Insilico Inc to test their lead molecules and find newer molecules to fight cancer and ageing. Their recent paper on "Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data" received editor choice award by American Chemical Society. They are known for their collaborative efforts to find newer and better solution for ageing and cancer.

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Signal Transduction Pathways

Signal Transduction Pathways
RTK, GPCR, GF, Cytokine, Wnt, Death Factors & Shh pathways