Cancer Treatments

Final Neoplasia Lecture and Cancer Treatments

Introduction

This lecture focuses on cancer treatments, expanding from previous years' brief coverage due to high student interest. It aims to provide a basic understanding of primary cancer therapies, including surgery, radiation, chemotherapy, and targeted treatments. The lecture also touches on personalized cancer medicine.

Aims of Cancer Treatment

Curative

• The primary aim is always to cure the patient.

• However, many cancers have a high risk of recurrence.

• Remission: A term used to describe the absence of cancer after treatment.

• A cure is often suggested only after a prolonged period of remission.

• Focus on cancers that haven't yet spread, with follow-up treatment to reduce recurrence risk.

• Early detection is crucial for achieving a curative stage.

Controlling Cancer and Remission

• This is the most likely outcome, especially for invasive or non-resectable cancers.

• Treatment aims to control the cancer and extend the patient's life.

Palliative Care

• For terminal patients, where the cancer is life-ending.

• Palliative Treatment: Focuses on extending life and improving the patient's comfort and quality of life.

Treatment Modalities

• Surgery

• Radiation Therapy (Radiotherapy)

• Chemotherapy

• Hormonal and Targeted Immunotherapies

Personalized Cancer Medicine (Precision Medicine)

• Aims to maximize treatment efficacy and minimize toxicity.

• Moves away from standardized treatments towards patient-centered approaches.

• Considers individual characteristics and the genetic profile of the patient's cancer.

Goals:

• Guide treatment options to be more specific and effective.

• Identify genes that predispose individuals to cancer and modify behaviors to prevent it.

• Utilize genetics and biological markers to tailor treatment.

• Profile the genetics of tumors to identify markers for targeted treatments.

Examples of Genes of Interest:

• BRAF: Associated with breast cancer, aiding prevention and treatment.

• KRAS: Associated with colorectal cancer, guiding treatment strategies.

• HER2: Significant in targeted treatment, particularly for HER2-positive breast cancer.

• EGFR (Epidermal Growth Factor Receptor): Often overexpressed in certain cancers, providing a target for treatments.

Examples of Personalized Cancer Medicine in Breast Cancer:

• Prevention: Testing for BRCA1 and BRCA2 mutations; considering tissue removal (breast and ovarian) for high-risk individuals.

• Treatment: Targeting HER2 overexpression with drugs like trastuzumab (immunotherapy using monoclonal antibodies).

Genetic Testing:

• Clinics are offering genetic testing to develop particular treatment plans based on individuals cancer markers.

Continuing Research:

• Aims to identify new markers for targeted treatments.

• Clinical trials are ongoing.

• Resistance to targeted treatments remains an issue, necessitating newer generation strategies.

Cancer Treatments

Surgery

• Used for tumor removal, diagnosis, staging, and genetic testing.

• Provides tissue samples for analysis.

• Removal of surrounding lymph nodes helps determine cancer spread.

Use cases:

• Helpful in personalised treatment, to tailor the treatment.

• In later stages, to relieve symptoms (palliation).

• First line of treatment for solid tumours for remission and cure.

Spread Considerations:

• If spread has occurred, surgery may reduce further spread and functional changes.

Radiation Therapy (Radiotherapy)

• Localized therapy using an ionizing radiation source to induce DNA damage in cancer cells.

• Aims to eradicate the cancer without excessive toxicity or damage to surrounding normal structures.

Mechanism of action:

• Works well in rapidly renewing cells.

Applications:

• Used for solid tumors and blood cancers.

Types of Radiotherapy:

• External: Uses a beam of ionizing radiation targeted at the cancer.

  • The machinery is becoming more precise.

  • Image-guided radiotherapy

  • Intensity modulated radiotherapy

• Internal (Brachytherapy): Infusion or internalization of a radioactive source.

External Beam Radiation Types:

• Conventional

  • Image Guided

  • Intensity Modulated

  • Proton Therapy

Side Effects:

Side effects depend on the cancer type and location.

• Bone marrow suppression

• Hair loss (particularly with head and neck cancers)

• Diarrhea

• Mucosal inflammation

• Nausea and vomiting

• Fatigue

• Weight loss

• Anemia

Systemic Effects:

• Overlap side effects of the cancer.

Chemotherapy

• Non-selective cytotoxic drugs that target vital cellular or metabolic processes.

• Disrupts malignant cell cycle and function, leading to cell death.

Mechanism of Action:

• Induce massive DNA damage to prevent cell division and promote apoptosis.

• Chemotherapy must eradicate enough tumor cells for the immune system to eliminate the rest.

Combination Chemotherapy:

• Combines multiple agents to reduce drug resistance.

• Each agent targets a different aspect of the cancer.

Example

• Combination of specific phase chemotherapeutic agents with general cell cycle agents to maximize tumour cell death

Examples of chemotherapeutic combinations

• Five fluorouracil + methotrexate

Cellular Resistance:

• A significant issue; surviving resistant cells can cause recurrence.

Adjuvant Chemotherapy:

• Administered after primary tumor removal to eliminate remaining cancer cells.

Neo-adjuvant Chemotherapy:

• Given before surgery or radiation to shrink the tumor and improve treatment options.

Categories of Chemotherapy Drugs:

General Theme of Chemos:

• Affect DNA replicative cell cycle function and force the cell through apoptosis or cell death.

Adverse Effects of Chemotherapy:

• Gastrointestinal Tract: Oral ulcers, malabsorption, nausea, vomiting, ulceration, severe diarrhea.

• Bone Marrow Suppression: Anemia, bleeding, immunosuppression.

• Alopecia: Hair loss (usually temporary).

• Skin Issues: Rashes, breakdown, dryness.

• Reproductive Tract Issues: Decreased fertility, premature menopause.

Supportive Care for Adverse Effects:

• Anti-emetic drugs, analgesia, nutritional supplements.

Targeted Treatments: Hormonal Therapies

• Tumors stimulated by the body's hormones (e.g., breast, prostate, ovarian cancers) are hormone dependants.

• Inhibiting hormones from reaching tumors can make treatments more effective or stimulate apoptosis.

Ways to Affect Tumors with Hormones:

• Block hormone production.

• Block pituitary signals.

• Fool signal pathways.

• Block cells' ability to read signals (antagonists of hormonal receptors).

Examples of Hormonal Therapy:

• Oestrogen Receptor Blockers: Tamoxifen blocks oestrogen function in breast cancers.

• Tamoxifen has side effects such as proliferation of endometrial tissue and hyperplasia.

Adverse Effects:

• Related to hormonal changes (nausea, menstrual irregularities, fluid retention, hot flashes, erectile dysfunction, changes in muscle mass).

Hormonal Treatments

Targeted Treatments

• Designed to bind with specific molecule targets to suppress tumor growth and stimulate apoptosis.

• This term encompasses a large range of drugs.

• More selective than cytotoxic drugs, with the goal of destroying cancer cells while sparing normal cells; some are successful.

Kinase Inhibitors:

• Block kinase enzyme pathways (phosphorylation).

• There are lots of examples.

Tyrosine Kinase Inhibitors:

Example: EGFR

• EGFR (Epidermal Growth Factor Receptor): A transmembrane regulatory molecule that activates intracellular tyrosine kinase associated to signals from the receptor to allow cell growth and proliferation. EGFR is overexpressed on cancer cells and associated to unregulated cell growth and a poor prognosis of cancer, suppressing proliferation with targeted drugs can improve conditions of lung cancer, breast cancer, and colon cancer.

Multi tyrosine kinase inhibitors: inhibit multiple tyrosine kinases, having great implications for the cell activity.

• BCR ABL Inhibitors: Used for chronic myeloid leukemia; e.g., imatinib.

• mTOR Kinase Inhibitors: Inhibit mTOR (mammalian target of rapamycin), leading to G1 cell cycle arrest and apoptosis.

• BRAF Kinase Inhibitors: For unresectable metastatic melanoma; inhibit proliferation and suppress tumor growth.

Adverse Effects:

• Gastrointestinal effects, skin problems, cardiotoxicity, myelosuppression (bone marrow activity is decreased).

Immunotherapy

• Eliminates cancer cells without damaging normal tissues by stimulating memory cells that provide long term protecting for tumor and metastatic cells.

• Manipulates the immune system to fight cancer more effectively.

Methods:

• Stimulate the immune system to work effectively against the cancer.

• Stimulate T cell anti cancer actions: Cytokine responses improves body's ability to respond to cancer.

• Provide vaccines against cancer.

• Administer a medication (antibody) that tags cancer cells for immune system identification and destruction.

Monoclonal Antibody Drugs:

• Antibodies produced to bind to specific antigens on the surface of cancer cells, leading to their destruction.

Examples:

• Rituximab: Treatment for lymphoma, binds B cells.

• Trastuzumab (Herceptin): Targets HER2 in breast cancer and inhibits cell replication.

Cancers differentiated by types of cancers for treatments:

• Solid Tumour

  • The varying types of cancers are lung, brain, bowel

• Blood Cancer (originate in the bone marrow)
  Leukaemia, Lymphoma, Myeloma

Cancer Treatments

Different types of cancers require different treatments

The state of metastasis can also influence cancer treatments.

Treatments for Solid Tumours:

• Remove the tumor.

Spread Considerations:

• Radiation, chemotherapy, can be used alone or in combination.

• The option of targeted treatments are based on market identification like the HER2 and EGFR.

Treatments for Haematological Cancers:

Blood cancer, Lymphoma, Myeloma are some of the Blood Cancers

The Haematological cancer is based on the bone marrow, where there isn't a solid tumour. The treatment varies quite a lot to the solid tumour treatment.

• Intense cycles of chemo and targeted therapy.

• Immunotherapies are used to try and suppress the treatment.

• Radiation may be utilised for treatment by ablating the stem cells.

• Bone marrow stem cell transplantation may be required