Book Volume 1
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Author: Shashank K. Singh, Reena Singh and Chirag Chopra
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List of Contributors
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Evolution of Cancer Therapies
Page: 1-23 (23)
Author: Sonali Verma, Gresh Chander, Deepika Bhushan Raina, Ruchi Shah and Rakesh Kumar*
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Cancer is commonly considered the “Pathology of the Century” assuming the associations of an endemic disease spread throughout the world. The beginning of the 20th century witnessed an improvement in the surgical techniques for tumorexcision, with the first abdominoperineal resection performed in 1908. Cancer treatment has been considered by its ups and downs throughout history, not only because of the side effect of treatments but also for the authenticity of cure and full remission, if any. In recent years, the first treatment of choice is immunotherapy with their significant therapeutic alternative. Nanotechnology is a new therapeutic replacement offering nanostructures for combining the treatment and imaging, targeted drug delivery, hyperthermia, and personalized, targeted therapy. Nowadays, gene therapy is contributing to a new approach to cancer treatment. These therapies can function independently or dependently with peptides, antibodies, folic acid, among others. In this chapter, we discuss the progression of cancer therapies and remedies, including immunotherapy, radiation, chemotherapy, surgery, nanomedicine, signalling pathway inhibitors and targeted gene therapy and their possible challenges.
Signaling Pathways in Oncotherapy
Page: 24-46 (23)
Author: Sonia Thapa, Arem Qayum, Jasvinder Singh, Tenzen Yodun and Shashank K. Singh*
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Cancer is the most dreadful disease and has significant health problems occurring worldwide. Cancer can arise from abnormal proliferation in a cell, and there are a diverse number of signaling pathways that regulate cell proliferation and its behavior. The signaling pathways contribute to the development and cellular homeostasis in cells. In diseases, especially cancer, developmental components of these pathways often become mutated or in many cases, overexpressed, which cause interruption or deregulation of cellular signaling. Cancer treatment action can target multiple signaling pathways and their molecular targets. This chapter provides an overview of the key pathways involved in tumor development and progression and components of the signaling pathways and their cross-talk associated with therapeutic implications.
Biomarkers for Cancer Therapy
Page: 47-58 (12)
Author: Indu Sharma, Jyotsna Sharma, Hemender Singh and Varun Sharma*
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Cancer is a complicated disease owing to its molecular heterogeneity, and adaptive resistance makes it even more complicated. Therefore, its exact mechanism needs to be inferred in order to obtain adequate treatment for the patients. Biomarkers present a robust approach in understanding the range of malignancies along with its applications in screening, clinical trials, diagnosis and prognosis. The main intention of cancer research and investigation is to find out biomarkers to facilitate early detection of cancers as well as devise individual therapies simultaneously. With the evolution of various omics- techniques like proteomics and genomics, it has become feasible to observe many crucial cellular pathways. These techniques have facilitated the detection of biomarkers as well as signalling molecules related to cellular metabolism.
Targeted Molecular Therapies in Cancer
Page: 59-101 (43)
Author: Prince Anand, Sourabh Soni and Yogendra S. Padwad
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Cancer has been a significant healthcare concern globally and is severely affecting various populations across continents with 18.1 million new cases and over 9 million deaths in 2018 alone. Several therapeutic approaches have been developed against various cancers like radiation therapy and cytotoxic chemotherapy to eliminate the tumor by physical/chemical-mediated damage to rapidly dividing tumor cells. To some extent, standard cytotoxic therapies have been successful in treating the disease, but they exhibit severe side effects and pose a threat to other fast-growing noncancerous cells. The risks associated with cytotoxic chemotherapy like obliteration of normal rapidly growing cells, induced cytotoxicity, and development of resistance led to the initiation of efforts to discover novel and effective alternate targeted treatment modalities. Pragmatic research endeavours have led to the development of a new area of treatment strategies termed ‘targeted therapies. This approach targets the molecular mechanism of tumor progression and rationally inhibits the abnormal expression of involved genes or pathways, exhibits less toxicity, and shows more efficiency as compared to the traditional treatment regime. This current chapter comprehensively outlines the requirement and role of targeted molecular therapies in cancer, their types, mode of action limitations and future scope. It will aid readers to understand the necessity of alternative treatment modalities in cancer, their effectiveness in contrast to traditional treatment approaches and the combinatorial effect of both the regimes upon requirement. The chapter also sketches the challenges and limitation of this approach and how researchers can overcome them to develop novel, precise and more competent targeted molecular therapies.
Immunotherapy – A New Pillar in Head and Neck Cancer Therapy
Page: 102-121 (20)
Author: Chirag Chopra and Sankar Jagadeeshan*
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Head and Neck cancer (HNC) frequently presents with poor prognosis and a high death rate. Furthermore, as the survival rates are low and the currently used treatment modalities are toxic, there is a marked need for more efficient therapeutic regimens. Immune system dysfunction plays a role in both the development and progression of HNC, highlighting the potential role for immunotherapy to improve outcomes in this disease. HNC shows immune evasion through multiple mechanisms and particularly creates an immunosuppressive microenvironment by causing activation of inhibitory immune cells, release of suppressive factors and reduction in tumor immunogenicity. Research on these suppressive and evasive mechanisms has enabled immunotherapies, some of which may potentially be successful. Currently in HNC, only immune checkpoint inhibitors have proven clinical efficacy in randomized phase III trials. This chapter summarizes current knowledge of the role of the immune system in HNC, and provides a comprehensive overview on the challenges during immunotherapy in HNC.
Combinatorial Approaches to Treat Cancer
Page: 122-142 (21)
Author: Arem Qayum*, Sonia Thapa, Jasvinder Singh and Shashank K. Singh
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One of the limitations of chemotherapy is the distinction between the normal and tumor cells, which leads to unfavorable side-effects. Ideally, combinatorial chemotherapy is preferred over single-agent chemotherapy because of synergistic effects of the combination. For cancer chemotherapy, the quantifiable parameters include the five-year and the ten-year survival rates, which can be considerably improved by administering combinatorial treatments. For treating cancer patients with drug combinations, at least one of the drugs should be FDA-approved as an anti-cancer drug. Such combinations are effective as well as affordable for most patients. Another significant advantage of combinations over monotherapies is that the combinations of drugs can target multiple cancer signaling proteins, making the overall therapy broadrange and less toxic. Due to the heterogeneity of tumors, there are increased chances of development of chemoresistance. A combinatorial approach towards treating cancers is the way forward to dealing with resistant tumors. This chapter outlines how the combinatorial-targeted therapies constitute a novel and promising perspective to cancer therapy, already leading to beneficial clinical effects.
Recent Innovations in Regenerative Medicine and Cancer Research
Page: 143-155 (13)
Author: Jasvinder Singh, Daljeet Singh Dhanjal, Arem Qayum, Gurinder Singh, Sonia Thapa, Tenzen Yodun and Shashank K. Singh*
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Cancer is the condition when the cells proliferate at uncontrollable rates and the wrong locations. Cancer research is a prime property in the real-estate of science with immense potential of success. Regenerative medicine deals with the regeneration of new cells to replace damaged or mutated cells, which requires the understanding of growth-related pathways and molecular mechanisms of tumorigenesis. Stem cells have proven useful in cancer therapies, at least in those cancers, for which the stem cell markers have been identified. Induced pluripotency is an amicable solution for the cancers in which these markers are not significantly expressed. Genetic reprogramming of somatic cells to produce stem cells has been a magic bullet for regenerative medicine. The chapter presents the salient aspects of regenerative medicine and the potential of stem cells for cancer therapies.
Applications of Molecular Imaging Techniques in Oncology
Page: 156-187 (32)
Author: Rafia Basit and Shashank K. Singh*
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Novel molecular imaging techniques are direct or indirect visualising methods which complement the various approaches be it diagnostic or therapeutic. These techniques are gaining immense recognition as they are proving to be a powerful tool with the scope of improving every aspect of cancer care. Molecular imaging is a non-invasive technique of visualising the molecules and events related to it that form the basis of human tumor biology. Today various advanced molecular enhancers have been developed for visualising the molecular events in the human body efficiently and accurately. These include Ultrasound, PET, SPECT, MRI and Optical imaging which may assist in the rapid and more efficient diagnosis and grading of tumors which are fundamental for early and productive therapeutic response. The smart molecular imaging techniques not only allow localisation of tumors but also detect the expression levels and the altered functions of distinct proteins. Imaging can also help in looking for various activities which are hallmarks of cancer such as apoptosis, angiogenesis, and metastasis that are responsible for its altered biology and their therapeutic response. “Smart” molecular probes developed in molecular imaging seem encouraging for their potential to visualise tumor lesions before its resection and after, without reinjecting the probe to monitor the outcome or the effects of its removal. Additionally, dual labelling with fluorescent dyes of molecular MR probes may instigate simultaneous assistance during surgical resection, thus augmenting complete removal and preservation of important structures. Therefore, a correct combination of therapeutic and diagnostic approach is the requisite need of the hour.
Computational Tools in Clinical Oncology
Page: 188-200 (13)
Author: Hemender Singh, Indu Sharma and Varun Sharma*
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With the advancement in the sequencing technology, diagnosis, and new treatment methods in the field of oncology arises some new challenges to analyze such big data generated as a result. These challenges also lead to alternative approaches by which it can be solved. One such approach is the use of computational technology in the field to analyze, predict and respond with high accuracy to the problem. With the use of many web-based and offline computational tools, it now becomes easier to analyze and predict the result with high accuracy that could not be possible by using the human brain only. This book chapter summarizes some of these such tools related to analyzing multi-omic cancer molecular data, biomarker discovery, digital pathology tools for diagnosis and image deconvolution tools in the field of clinical oncology.
Theranostic Approaches for Combating Cancers
Page: 201-232 (32)
Author: Preeti Solanki*, Chayanika Putatunda and Rashmi Sharma
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Cancer theranostics has witnessed the new era translational medicine leading to the development of new treatment possibilities for cancer patients. The approach of ‘one-size-fits-all’ has changed from traditional methods of surgery, chemo- and radiotherapy to that of personalised cancer medicine, molecular targeted therapy, cancer immunotherapy, nanomedicine, alternative medicine and integrative therapy. The clinical trials for cancer drugs have complicated, requiring better regulatory and health policies, and collaborative efforts from the stakeholders involved in cancer drug discovery and development. A lot has been achieved, mainly in terms of knowledge and biological data, and the same is needed to be integrated and implemented into the development of successful cancer theranostics. The tumour heterogeneity still poses a challenge for scientists, but the last decade has paved a concrete pathway for the future in precise and personalised cancer therapy.
Nutritional Aspects of Cancer Therapy
Page: 233-251 (19)
Author: Chirag Chopra*, Daljeet Singh Dhanjal, Raja B.M. Tripathi, Saurabh Singh and Reena Singh
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It is essential to be aware of the advances in the nutritional aspects of cancer for oncology practitioners. Unlike the popular myth, the term “Cachexia” more effectively defines the present status in oncology patients rather than “cancer-related malnutrition” (CRM). The consensus guidelines recommend the usage of management algorithm, staging of the CRM involving screening for the nutritional risk and also devising a management strategy consistent with a phenotype and the staging. There should be an inclusion of preventive measures for the CRM in the management algorithm like pharmacological and non-pharmacological interventions aiming both anabolic and the anti-catabolic measures as well as repeated checking of the status of Nutrition. At present, the multimodal mechanism is the optimum method to battle catabolic resulting in CRM. This method should be simultaneously given with anticancer treatments and involve pharmaconutrients, nutritional intervention and the multiple target drug treatments and physical activity. This article provides the practitioners with an awareness of the recent development in the area of nutritional care and as well as defined guidelines to regulate cancer therapy during treatment. This book chapter thus gives insightful guidelines pointing on crucial aspects of Nutrition for cancer treatment.
Traditional Medicine: Recognize Potential Cancer Treatments of Herbal Origin
Page: 252-267 (16)
Author: Pooja Thakur, Chirag Chopra and Reena Singh*
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Globally, cancer has become a second major cause of human mortality rate, which significantly affects the human population. Therefore a constant demand is kept for new therapies to treat and cure this severe disease. Due to less toxic side effects in comparison to existing treatment such as chemotherapy, herbal medicine has been drawn consideration in many disease cure and treatment. Now with due attention, traditional medicine from herbal plants are admired for cancer treatment as of their potent anticancer effects. Plant secondary metabolites such as polyphenols, flavonoids, among others, have potent anti-cancer properties and have been explored for cancer treatment for centuries. Many studies have revealed that these secondary metabolites possess effective anticancer activities by exhibiting several different mechanisms such as; antioxidant activity, apoptosis induction, target specificity, prevention to DNA damage, cell cycle regression, angiogenesis prevention. Therefore, herbal plants and their naturally derived compounds become potential drugs for cancer cure and treatment.
Himalayan Herbal Medicine for Cancer
Page: 268-288 (21)
Author: Daljeet S. Dhanjal, Chirag Chopra and Reena Singh
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Traditional medicine and natural products have recently gained interest and have become a matter of great importance. The traditional medicines are rooted to Ayurveda, Traditional Chinese medicine, traditional Korean medicine, Kampo and Unani, which were practised previously and are still used in a few parts of the world. Plants are a vital source of herbal and synthetic agents used by various pharmaceutical industries. Some plant metabolites have found clinical applications as anti-cancer agents such as paclitaxel (taxol), topotecan, vinblastine and vincristine. In India, Himalayas is one of the world biodiversity hotspots harbouring various pervasive medicinal plants. Despite comprehending of the literature regarding ethnopharmacological information of medicinal plant, but information of some pervasive medicinal plant is still being exploited. In the past few decades, herbal medicine has gained popularity worldwide and emerged as the opportunity to promote traditional Indian medicine globally. Now, people from various developing and developed countries have gained interest in Himalayan herbal medicines. Hence, this chapter aims to provide an overview about the importance of herbal medicine and provide the information about the medicinal plants with anti-cancerous potential.
Ayurveda: A Promise of Nature
Page: 289-311 (23)
Author: Tenzen Yodun, Sonia Thapa and Shashank K. Singh*
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Ayurveda involves a variety of scientific bases of harmony as well as wellbeing. The origin of Ayurveda can be traced to the ancient knowledge in Rigveda and many more. Since ancient times, Ayurveda is a traditionalistic, conservative healthcare system of Indian medicine. Many ayurvedic medicines have been exploiting for the treatment and management of various ailments in human beings. Several drugs have been developed from Ayurveda and known as 'tradition to trend'. The potential of ayurvedic drugs needs to be explored further with scientific validation approaches for better therapeutic leads. This chapter proposed the various aspects of Ayurveda and drug discovery approaches for its development and therapeutic approaches.
Yoga: A Consolidated Approach to Treat Cancer
Page: 312-323 (12)
Author: Manoj Kumar Jena*
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The practice of Yoga is mainly adopted to keep harmony between the body and the mind. The literal meaning of Yoga is ‘union’, which means union of the body and the mind. Various body postures with meditation and breathing exercises are a part of Yoga, and this practice is performed in India for thousands of years. Ashtanga Yoga includes eight limbs or eight stages of Yoga which helps in attaining mental, physical, and spiritual well-being in humans by regularly practising it. Yoga practice can cure many diseases, and it is beneficial in cancer patients who have received chemotherapy and radiation therapy. Fatigue, body pain, psychological stress is associated with cancer patients undergoing therapies, and Yoga practice is found to alleviate these symptoms in patients and promotes quick recovery. Many randomized control trials have been done to show the beneficial effects of Yoga in cancer patients, irrespective of the type of cancer that caused the disease. This chapter discusses the effects of Yoga practice in cancer patients and underscores the importance of Yoga in cancer therapy.
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The advancements in molecular marker discovery, genomics, transcriptomics and proteomics in recent years have enabled researchers to develop targeted therapies against cancers. Cancer research and management is multi-disciplinary and multimodal. In addition to conventional chemotherapy and radiotherapy, targeted immunotherapy has also provided considerable success in the clinic. There is also scientific evidence on the impact of alternative therapies on cancer patients. Modern Cancer Therapies and Traditional Medicine: An Integrative Approach to Combat Cancers summarizes the general aspects of cancer therapy and management. Chapters cover cancer medicine in two broad sections, the book presents comprehensive information on a diverse range of cancer treatments. The first section covers conventional molecular oncology and therapy including targeted therapies, immunotherapies, cancer signaling pathways and the use of computational techniques. The second section focuses on traditional methods of treatment including the role of nutrition, traditional medicine, Yoga and Ayurveda in cancer prevention and management. The book is an accessible update of the state of the art in cancer diagnostics and therapy for students and academicians at all levels.