Treatment Strategies in Cancer

An overview of the main treatment strategies that can be used for the treatment of cancer, including a discussion of their respective advantages and disadvantages

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Cancer can be treated using a number of different treatment strategies1

The choice of strategy is dependent on the type and stage of cancer1

Treatment strategies for cancer have become more targeted for cancer cells over time.2 The timeline below shows chronological developments for the main cancer treatment strategies

Cancer Treatment Strategy Timeline2-5

Figure adapted from Figure 2 in Falzone L, et al. 2018.2

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Surgery

Surgery involves the physical removal of the cancer from the body. It can be used to6:

  • Remove the entire tumor
  • Debulk a tumor to allow other treatments to be more efficacious
  • Ease cancer symptoms associated with pain or pressure

Advantage

Surgery can be used to treat many types of cancer, particularly those with solid tumors that are contained within one area6

Disadvantage

Surgery may promote cancer recurrence or the progression of metastatic disease.7,8 This is a risk in cases where residual cancer cells are left in the patient following surgery

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A mastectomy is a type of surgery used for the treatment of breast cancer. It involves surgically removing part of the breast or the entire breast, and possibly some of the surrounding tissues9

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Hormonal Therapy

Hormonal therapy can be used to treat patients whose cancers are hormone dependent and express high levels of hormone receptors10

Cancers that may be appropriate for hormonal therapy include breast, prostate, endometrial, and uterine cancers10,11

There are two main approaches to hormonal therapy12,13:

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Advantages

In hormone receptor-positive cancers such as breast cancer, hormonal therapies have resulted in significant decreases in cancer-related mortality11,14

Some hormonal therapies can be used for cancer prevention in high-risk individuals15

Disadvantages

Altering the balance of hormones can cause side effects, such as menopausal symptoms, bone thinning, and loss of interest in sex12,16

Some hormonal therapies may need to be taken over a long period of time (e.g. 5–10 years in the case of breast cancer), and treatment adherence can be low17,18

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Tamoxifen is used for the treatment and prevention of estrogen receptor-positive breast cancer.13,14 It inhibits estrogen activity by binding to the estrogen receptor13

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Radiation Therapy

Radiation therapy is one of the most common treatments for cancer.19 It is used to destroy or damage cancer cells and shrink tumors19,20

Radiation therapy can be used to treat cancer or ease cancer symptoms, such as pain, breathing, or swallowing difficulties19,20

Mechanism of Action19,20

High-energy particles or waves, such as X-rays, gamma rays, electron beams, or protons, are applied to the cancerous area

This results in small breaks in the DNA inside cells

These breaks prevent cancer cells from growing and dividing, eventually resulting in cell death

Advantage

Radiation therapy is a local treatment and is applied only to the part of the body that contains cancer cells19

Disadvantage

It is not designed to specifically target cancer cells; therefore, it damages not only cancer cells but also nearby normal cells19

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Radiation therapy is recommended for the treatment of head and neck cancers21

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Chemotherapy

Chemotherapy uses drugs to stop or slow the growth of quickly dividing cancer cells22

Advantage

Many chemotherapy drugs have resulted in the successful treatment of different types of cancer, either alone or in combination with other drugs or treatments23,24

Disadvantages

Chemotherapy is not designed to specifically target cancer cells; hence, it kills or slows the growth of both cancer and healthy cells22

Damage to healthy cells may cause side effects, such as mouth sores, nausea, and hair loss, that often resolve after treatment has finished22

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Cisplatin is approved for the treatment of multiple cancer types, such as advanced testicular, ovarian, and bladder cancer25

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Targeted Therapy

Targeted therapy blocks the growth and spread of cancer by interfering with specific molecular targets that are associated with these processes in cancer cells26

Most targeted therapies are either small molecules or monoclonal antibodies26

Advantage

Unlike chemotherapy, targeted therapy is designed to target cancer cells with minimal impact on normal healthy cells26,27

Disadvantage

Cancer cells may become resistant to the treatment.26 Therefore, for most cancers, targeted therapy is used in combination with other targeted therapies or with other cancer treatments, like chemotherapy, surgery, and/or radiation therapy26,27

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Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. This growth factor has a role in a major molecular pathway implicated in tumor growth for renal cell carcinoma (RCC).28 Bevacizumab is recommended as first-line treatment for metastatic RCC28

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Figure adapted from Figure 1 in Alesini D, et al. 2015.28
DNA, deoxyribonucleic acid; 4E-BP1, eukaryotic initiation factor 4E-binding protein 1; HIF, hypoxia-inducible factor; mTOR, mammalian target of rapamycin; S6K1, ribosomal protein S6 kinase 1; VEGF, vascular endothelial growth factor; VEGFR-2, VEGF receptor-2.

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Immunotherapy

Immunotherapy is a biological therapy that helps the body’s immune system fight cancer29

Some immunotherapies mark cancer cells so that they can be targeted by the immune system, while others boost the overall immune system to provide a durable immune response29,30

The main types of immunotherapies now being used to treat cancers include31,32:

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Advantage

Because immunotherapies target the immune system, they can be used in the treatment of multiple types of tumors33

Disadvantage

Immunotherapies can produce negative regulation and lead to autoimmune diseases33

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Pembrolizumab and nivolumab are immune checkpoint inhibitors that inhibit programmed cell death receptor-1 (PD-1). They are used to treat several types of cancer, including34-36:

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Gene Therapy

Gene therapy is a technique that uses genes to treat or prevent diseases37

  • As of December 2019, over 65% of gene therapy clinical trials are focused on the treatment of cancer38
  • Currently, there are some approved gene therapies for the treatment of cancer39

Advantage

Gene therapy can target cancer cells specifically, which decreases the likelihood of systemic adverse effects40

Disadvantage

Low-transduction efficiency and potential toxicity associated with viral delivery40,41

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Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, has been approved for the treatment of B-cell acute lymphoblastic leukemia and B-cell lymphoma3

Axicabtagene ciloleucel, another CAR T-cell therapy, has been approved for the treatment of B-cell lymphoma42

Other Cancer Treatments

There are a number of other procedures that can be used for the treatment of cancer43-48

HIGH-INTENSITY FOCUSED ULTRASOUND

The application of an ultrasound beam that propagates through soft tissue as a high-frequency pressure wave, resulting in the death of cancer cells43

CRYOTHERAPY

The use of extreme cold, produced by liquid nitrogen or argon gas, to freeze and destroy tumor tissue.44 For external tumors, liquid nitrogen can be applied directly to the area. For internal tumors, a hollow instrument containing liquid nitrogen or argon gas (known as a cryoprobe) is used

PHOTODYNAMIC THERAPY

The administration of a photosensitizing drug to a patient, followed by irradiation of their tumor with light at a wavelength corresponding to the drug’s absorbance band.45 This irradiation results in drug activation and, in the presence of oxygen, triggers subsequent tumor cell death

LASER TREATMENT

The use of a laser to destroy abnormal or cancerous cells. It is most often used for superficial and early stage cancers46

RADIOFREQUENCY ABLATION

The application of an alternating current to a tumor via a needle electrode. This leads to agitation and heating of the tissue surrounding the needle and subsequent cell death47

ELECTRO-CHEMOTHERAPY

The administration of a poorly permeant chemotherapy, followed by electroporation of the tumor site. Electroporation results in increased permeability of the cancer cell membranes, thus allowing the chemotherapeutic drug to enter cells and elicit its cytotoxic effects48

References

  1. National Institutes of Health. Types of cancer treatment. Available at: https://www.cancer.gov/about-cancer/treatment/types. Accessed September 23, 2020.
  2. Falzone L, et al. Front Pharmacol 2018;9:1300.
  3. Kymriah® [package insert]. 2018. Available at: https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---KYMRIAH.pdf. Accessed September 24, 2020.
  4. Yescarta® [package insert]. 2020. Available at: https://www.fda.gov/media/108377/download. Accessed September 24, 2020.
  5. Love RR, Philips J. J Natl Cancer Inst 2002;94(19):1433–1434.
  6. National Cancer Institute. Surgery to treat cancer. Available at: https://www.cancer.gov/about-cancer/treatment/types/surgery. Accessed October 14, 2020.
  7. Hiller JG, et al. Nat Rev Clin Oncol 2018;15(4):205–218.
  8. Tohme S, et al. Cancer Res 2017;77(7):1548–1552.
  9. MedlinePlus. Mastectomy. Available at: https://medlineplus.gov/mastectomy.html. Accessed October 12, 2020.
  10. Fairchild A, et al. AJR Am J Roentgenol 2015;204(6):W620–W630.
  11. Abraham J, Staffurth J. Medicine 2020;48(2):103–107.
  12. National Cancer Institute. Hormone therapy to treat cancer. Available at: https://www.cancer.gov/about-cancer/treatment/types/hormone-therapy. Accessed September 30, 2020.
  13. National Cancer Institute. Hormone therapy for breast cancer. Available at: https://www.cancer.gov/types/breast/breast-hormone-therapy-fact-sheet. Accessed October 1, 2020.
  14. Tremont A, et al. Ochsner J 2017;17(4):405–411.
  15. Crew KD, et al. NPJ Breast Cancer 2017;3:20.
  16. Cancer Research UK. Side effects of hormone therapy in women. Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/hormone-therapy/side-effects-women. Accessed September 30, 2020.
  17. American Cancer Society. Hormone therapy for breast cancer. Available at: https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html. Accessed September 30, 2020.
  18. Harrow A, et al. BMJ Open 2014;4(6):e005285.
  19. American Cancer Society. How radiation therapy is used to treat cancer. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/basics.html. Accessed October 14, 2020.
  20. National Cancer Institute. Radiation therapy to treat cancer. Available at: https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy. Accessed September 28, 2020.
  21. Pfister DG, et al. J Natl Compr Canc Netw 2020;18(7):873–898.
  22. National Cancer Institute. Chemotherapy to treat cancer. Available at: https://www.cancer.gov/about-cancer/treatment/types/chemotherapy. Accessed October 14, 2020.
  23. Sudhakar A. J Cancer Sci Ther 2009;1(2):1–4.
  24. American Cancer Society. How chemotherapy drugs work. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html. Accessed September 24, 2020.
  25. Cisplatin [package insert]. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018057s089lbl.pdf. Accessed September 28, 2020.
  26. National Cancer Institute. Targeted cancer therapies. Available at: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet. Accessed September 24, 2020.
  27. American Cancer Society. How targeted therapies are used to treat cancer. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/targeted-therapy/what-is.html. Accessed September 24, 2020.
  28. Alesini D, et al. Ther Adv Urol 2015;7(5):286–294.
  29. National Cancer Institute. Immunotherapy to treat cancer. Available at: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy. Accessed September 24, 2020.
  30. Joshi S, Durden DL. J Oncol 2019:5245034.
  31. American Cancer Society. How immunotherapy is used to treat cancer. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html. Accessed September 24, 2020.
  32. National Cancer Institute. Immune system modulators. Available at: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/immune-system-modulators. Accessed October 13, 2020.
  33. Tan S, et al. Biomed Pharmacother 2020;124:109821.
  34. American Cancer Society. Immune checkpoint inhibitors and their side effects. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed September 24, 2020.
  35. Libtayo® [package insert]. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761097s000lbl.pdf. Accessed October 9, 2020.
  36. Keytruda® [package insert]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761097s000lbl.pdf. Accessed October 9, 2020.
  37. National Institutes of Health. What is gene therapy? Available at: https://ghr.nlm.nih.gov/primer/therapy/genetherapy. Accessed September 24, 2020.
  38. Journal of Gene Medicine. Gene therapy clinical trials worldwide. Available at: http://www.abedia.com/wiley/indications.php. Accessed September 24, 2020.
  39. Ginn SL, et al. J Gene Med 2018;20(5):e3015.
  40. Wirth T, Yla-Herttuala S. Biomedicines 2014;2(2):149–162.
  41. Das SK, et al. J Cell Physiol 2015;230(2):259–271.
  42. U.S. Food and Drug Administration. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma. Accessed September 24, 2020.
  43. Ning Z, et al. Onco Targets Ther 2019;12:1161–1170.
  44. National Cancer Institute. Cryosurgery in cancer treatment. Available at: https://www.cancer.gov/about-cancer/treatment/types/surgery/cryosurgery-fact-sheet. Accessed October 1, 2020.
  45. Agostinis P, et al. CA Cancer J Clin 2011;61(4):250–281.
  46. National Cancer Institute. Lasers in cancer treatment. Available at: https://www.cancer.gov/about-cancer/treatment/types/surgery/lasers-fact-sheet. Accessed October 1, 2020.
  47. Gillams AR. Br J Cancer 2005;92(10):1825–1829.
  48. Esmaeili N, Friebe M. J Healthc Eng 2019:2784516.