SECTION II: Anticancer Therapeutics 4 Introduction to Anticancer Therapeutics Teni Boulikas 4.1 Problems in cancer 4.2 Cancer treatments 4.3 Classification of chemotherapy drugs 5 Platinum Drugs Teni Boulikas, Alexandros Pantos, Evagelos Bellis and Petros Christofis 5.1 Cisplatin 5.2 Lipoplatin 5.3 Carboplatin 5.4 Oxaliplatin 5.5 — Lipoxal 5.6 New Platinum Compounds 5.7 Cisplatin Resistance and Chemotherapy 6 Antimicrotubule Agents Iain Brown, Jay N Sangrithi-Wallace and Andrew C Schofield 6.1 Taxanes 6.2 Vinca Alkaloids 6.3 Mechanisms of Resistance to Antimicrotubule Agents 7 Antimetabolites in Cancer Therapy Jessica Scaife and David Kerr 7.1 Introduction 7.2 Folate Antagonists 7.3 Pyrimidine Antagonists 7.4 Purine Antagonists 7.5 Summary 8 Antitumour Antibiotics Manuel M. Paz 8.1 Introduction 8.2 Actinomycin 111 8.3 Mitomycin C 112 8.4 Bleomycin 115 8.5 Anthracyclines 118 8.6 Trabectedin (Ecteinascidin, ET-743) 121 8.7 Camptothecins 123 8.8 Podophyllotoxins 124 9 Alkylating Agents Ana Paula Francisco, Maria de Jesus Perry, Rui Moreira and Eduarda Mendes 9.1 Introduction 133 9.2 Nitrogen Mustards 133 9.3 Methylmelamines and Ethylenimines 140 9.4 Methylhydrazine Derivatives. 141 9.5 Alkylsulfonates 143 9.6 Nitrosoureas 144 9.7 Triazenes 149 10 Hormone Therapies George C. Zografos, Nikolaos V. Michalopoulos and Flora Zagouri 10.1 Introduction 159 10.2 Oestrogen Receptor Targeted Therapeutics 160 10.3 Progesterone-Targeted Therapy 174 10.4 Neuroendocrine Tumours 176 11 Photodynamic Therapy of Cancer K. Eszter Borbas and Dorothée Lahaye 11.1 Introduction 187 11.2 Photosensitizers 196 11.3 Outlook 212 11.4 Acknowledgement 212 12 Target-directed Drug Discovery Tracey D. Bradshaw 12.1 Introduction 223 12.2 Tyrosine Kinases - Role and Significance in Cancer 226 12.3 Targeted Therapy for the Treatment of Non-small Cell Lung Cancer (NSCLC) 226 12.4 Targeted Therapy for the Treatment of Chronic Myeloid Leukaemia 229 12.5 Targeted Therapy for the Treatment of Breast Cancer 230 12.6 Angiogenesis 231 12.7 Targeting Cell Cycling 12.8 Targeting Apoptosis 12.9 Targeting mTOR 12.10 The Future of Molecularly Targeted Therapy 13 Tumour Hypoxia: Malignant Mediator Jill L. O'Donnell, Aoife M. Shannon, David Bouchier-Hayes 13.1 Introduction 13.2 Hypoxia Inducible Factor-1 and Hypoxia HIF-10 Post-translational Changes 13.3 How Genetics Can Modify HIF 13.4 How Tumours Overcome Hypoxia with HIF-1 13.5 HIF-1 Therapeutics 13.6 Conclusion 14 Resistance to Chemotherapy Drugs Robert O'Connor and Laura Breen 14.1 Introduction 14.2 What are the Factors Limiting the Efficacy of Cancer Chemotherapy Treatment? 14.3 A Classification of the Important Chemotherapy Resistance Mechanisms 14.4 Illustrative Mechanisms of Pharmacokinetic Resistance 14.5 Illustrative Mechanisms of Pharmacodynamic Resistance 14.6 Conclusion 15 Cancer Immunotherapy Maria Belimezi 15.1 The Molecular Basis of Cancer Immunotherapy and Gene Immunotherapy of Cancer 15.2 Recombinant Monoclonal Antibodies 15.3 Cell Immunotherapy 15.4 Cancer Vaccines 16 Gene Therapy Maria Belimezi, Teni Boulikas and Michael L. Roberts 16.1 The Concept of Gene Therapy 16.2 Steps for Successful Gene Therapy 16.3 Retroviruses in Cancer Gene Therapy 16.4 Adenoviruses in Cancer Gene Therapy 16.5 Gene Therapy of Cancer 16.6 Cancer Immunotherapy with Cytokine Genes 16.7 IL-12 in Cancer Immunotherapy 16.8 Viruses able to Kill Cancer Cells 17 Antisense Agents Huma Khan and Sotiris Missailidis 17.1 Introduction 17.2 Traditional Antisense Oligonucleotides (ASOs) 17.3 Ribozymes and DNAzymes 17.4 RNA Interference and siRNAs 17.5 Shortcomings of Antisense Therapeutics 17.6 Antisense Agents in Clinical Trials 17.7 Concluding Remarks 18 Aptamers as Anticancer Agents Vaidehi Makwana, Suzanne Simmons and Sotiris Missailidis 18.1 Introduction 18.2 Aptamers in Cancer 18.3 Final comments
Key Takeaways
- Platinum-based chemotherapy drugs are a major class of anticancer therapeutics.
- Antimicrotubule agents like taxanes and vinca alkaloids target cell division processes in cancer cells.
- Hormone therapies play an important role in treating certain types of cancers.
Practical Tips
- Understanding the classification of chemotherapy drugs can help in choosing appropriate treatments for different types of cancer.
- Photodynamic therapy is a promising approach that uses light to activate photosensitizers and kill cancer cells.
- Gene therapy offers potential new avenues for treating cancer by targeting specific genetic mutations.
Warnings & Risks
- Resistance to chemotherapy drugs can significantly limit their effectiveness in treating cancer.
- Cancer immunotherapy may have side effects such as cytokine release syndrome or immune-related adverse events.
- The use of viruses in gene therapy must be carefully managed to avoid unintended consequences.
Modern Application
While the chapter focuses on traditional anticancer therapeutics, many of these principles remain relevant today. Advances in targeted therapies and immunotherapy have expanded treatment options but understanding foundational chemotherapy drugs is still crucial for effective cancer management.
Frequently Asked Questions
Q: What are some common platinum-based drugs used in treating cancer?
Common platinum-based drugs include Cisplatin, Lipoplatin, Carboplatin, and Oxaliplatin. These drugs work by forming cross-links with DNA to inhibit cell division.
Q: How do antimicrotubule agents like taxanes affect cancer cells?
Taxanes stabilize microtubules in the mitotic spindle, preventing proper chromosome segregation and leading to cell death. This is particularly effective against rapidly dividing cancer cells.
Q: What role does gene therapy play in modern anticancer treatments?
Gene therapy can target specific genetic mutations or pathways involved in cancer progression, offering a personalized approach to treatment that may be more effective than traditional chemotherapy.